CN103720689A - Use of transforming growth factor (TGF)-beta1 inhibitor in lung cancer treatment - Google Patents
Use of transforming growth factor (TGF)-beta1 inhibitor in lung cancer treatment Download PDFInfo
- Publication number
- CN103720689A CN103720689A CN201410004597.7A CN201410004597A CN103720689A CN 103720689 A CN103720689 A CN 103720689A CN 201410004597 A CN201410004597 A CN 201410004597A CN 103720689 A CN103720689 A CN 103720689A
- Authority
- CN
- China
- Prior art keywords
- tgf
- cell
- lung cancer
- inhibitor
- beta1
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention discloses use of a transforming growth factor (TGF)-beta1 inhibitor in lung cancer treatment. The TGF-beta1 inhibitor inhibits a TGF-beta1 channel to increase the radiosensitivity of lung cancer cells. Through the manner, according to the use of the TGF-beta1 inhibitor in lung cancer treatment, the sensitivity enhancement effect of the TGF-beta1 inhibitor on the lung cancer cells is caused by inhibition on non-homologous end joining repair of deoxyribonucleic acid (DNA) double-strand break, change of cycle distribution of the lung cancer cells after irradiation, and obvious reduction of tumor growth by the TGF-beta1 inhibitor combined with X-ray treatment of 5Gy. The DNA repair capacity can be reduced by inhibition on the TGF-beta1 channel of tumor cells before irradiation, the cell cycle distribution is changed, the cell cloning ability is reduced, the tumor growth is delayed, and effective auxiliary means are provided by inhibiting the TGF-beta1 channel as radiotherapy of a patient with a lung cancer.
Description
Technical field
The present invention relates to lung cancer therapy field, particularly relate to the purposes of a kind of TGF-β 1 inhibitor in lung cancer therapy.
Background technology
Along with China's lung cancer morbidity rate rises year by year, pulmonary carcinoma has become one of malignant tumor to China people health threat maximum at present.Radiotherapy is to damage and kill tumor cell by free radical of ionizing radiation sedimentary energy and generation in tumor tissues etc., be a kind of main clinical treatment method, but the difference of radiosensitivity for tumor cell has caused radiocurable success rate to be protected.
Transforming growth factor-beta 1 (TGF-β 1) plays an important role in the dynamic equilibrium that regulates cell and tissue comprises the signal path of propagation, differentiation, migration, cell survival and angiogenesis etc., under normal circumstances, it is mainly by maintaining the dynamic equilibrium of cell and tissue to the transcriptional control of related gene.As an antioncogene, all there is change in the normal function of TGF-β 1 conventionally in tumor cell, and this mainly comes from the interaction between sudden change and the oncogene of its receptor or passageway related genes.The function that forms later stage TGF-β 1 and also can promote tumor growth in tumor, tumor cell self just can discharge a large amount of active TGF-β 1, and what this may be conducive to tumor invades profit, transfer, angiogenesis and the inhibition to anticancer immunologic function.Its this two-sided functional makes it likely as the target of oncotherapy.
Remove outside the regulating and controlling effect of dynamic equilibrium of cell growth, TGF-β 1 also regulating cell to genotoxicity stress in play an important role.Research finds to suppress TGF-β 1 path can suppress epithelial cell replying DNA damage, thereby comprising suppressing the activity of ATM and ATR, the phosphorylation that weakens Chk2, Rad17 and p53 and increase the radiosensitivity of cell, this indication suppresses TGF-β 1 path and is likely used to improve the success rate of tumour radiotherapy.In fact, research has confirmed that cell is subject to process with TGF-β 1 pathway inhibitor LY364947 according to front, thereby can increase the radiosensitivity of breast cancer cell by slowing down DNA damage reparation and reducing cloning efficiency, another kind of TGF-β 1 pathway inhibitor LY2109761 and ionizing radiation synergism have also delayed the growth of tumor in vivo.In addition, vivo and vitro experiment also shows that LY2109761 can increase the radiosensitivity of glioblastoma multiforme.
Radiotherapy in lung cancer maximal dose used is limited to the toleration of lung tissue around, and the common adverse effect that lung cancer patient stands after radiotherapy is exactly injury of lung and pulmonary fibrosis.And research has shown that lung carcinoma cell is subject to shine the TGF-β 1 of rear a large amount of releases and damage and the fibrosis of normal lung tissue are closely related.Research is also found, utilizes the rising of 4 weeks interior plasma TG F-β 1 after Patients Treated by Radiotherapy can predict exactly whether nonsmall-cell lung cancer patient has the danger of concurrent lung radiation injury toxicity (RILT).Therefore, TGF-β 1 can be used as an effective target of prevention RILT.And existing having studies show that Radix Et Rhizoma Rhei extract can reduce RILT by the level that reduces TGF-β 1 and IL-6, and improve pulmonary function.On the other hand, for studies show that of breast carcinoma and glioblastoma multiforme, suppressing TGF-β 1 path can increase the radiosensitivity of these tumor cells.But up to the present, suppressing TGF-β 1, whether to increase the radiosensitivity of lung carcinoma cell unclear.
Summary of the invention
The technical problem that the present invention mainly solves is to provide the purposes of a kind of TGF-β 1 inhibitor in lung cancer therapy, by suppressing the effective supplementary means of TGF-β 1 path as lung cancer patient radiotherapy.
For solving the problems of the technologies described above, the technical scheme that the present invention adopts is: the purposes of a kind of TGF-β 1 inhibitor in lung cancer therapy is provided, and described TGF-β 1 inhibitor suppresses TGF-β 1 path increases the radiosensitivity of lung carcinoma cell.
In a preferred embodiment of the present invention, described TGF-β 1 inhibitor is SB431542, and described lung carcinoma cell is p53 wild type Lines H460.
In a preferred embodiment of the present invention, described TGF-β 1 inhibitor is relevant with the p53 state of lung carcinoma cell to the radiosensitivity effect of lung carcinoma cell.
In a preferred embodiment of the present invention, the effect of described TGF-β 1 inhibitor is by changing DDR damage responsing reaction, suppressing the ability of non-homogeneous end DNA plerosis two strands and change cell cycle distribution to realize.
The invention has the beneficial effects as follows: the purposes of TGF-β 1 inhibitor of the present invention in lung cancer therapy, TGF-β 1 inhibitor is the non-homogeneous end link reparation that has suppressed DNA double chain interruption due to it to the enhancement effect of lung carcinoma cell, changed lung carcinoma cell in the period profile being subject to after photograph, the X ray of TGF-β 1 inhibitor associating 5Gy is processed the growth that has obviously reduced tumor.At the TGF-β of pre-irradiation inhibition tumor cell 1 path, can reduce its DNA damage repair ability, change cell cycle distribution, reduce Cell clonality, delay the growth of tumor, by suppressing the effective supplementary means of TGF-β 1 path as lung cancer patient radiotherapy.
Accompanying drawing explanation
In order to be illustrated more clearly in the technical scheme in the embodiment of the present invention, below the accompanying drawing of required use during embodiment is described is briefly described, apparently, accompanying drawing in the following describes is only some embodiments of the present invention, for those of ordinary skills, do not paying under the prerequisite of creative work, can also obtain according to these accompanying drawings other accompanying drawing, wherein:
Fig. 1 is the block diagram of TGF-β 1 impact of inhibitor SB431542 on H1299 cell proliferation of the present invention;
Fig. 2 is the block diagram of TGF-β 1 impact of inhibitor SB431542 on H460 cell proliferation of the present invention;
Fig. 3 is subject to the cloning efficiency figure after photograph through the H1299 cell of SB431542 processing or blank;
Fig. 4 is subject to the cloning efficiency figure after photograph through the H460 cell of SB431542 processing or blank;
Fig. 5 be H460 cell have or not under SB431542 pretreatment, be subject to 2GyX-roentgenization after the immunofluorescence photograph of 53BP1 foci of 1 h;
Fig. 6 be through SB431542 process or the H460 cell do not processed be subject to according to after the dynamic variation figure of 53BP1 foci number;
Fig. 7 be H460 cell have or not under SB431542 pretreatment, be subject to 2GyX-roentgenization after the immunofluorescence photograph of DNA-PKcs foci of 1 h;
Fig. 8 be through SB431542 process or the H460 cell do not processed be subject to according to or be not subject to according to after the positive cell rate containing DNA-PK foci dynamic variation figure;
Fig. 9 is the variation diagram of four groups of nude mices gross tumor volume after different disposal;
Figure 10 is the variation diagram that irradiation group and SB431542 combine irradiation group gross tumor volume after processing;
Figure 11 is the gross tumor volume variation diagram of each group of every nude mice after different disposal.
The specific embodiment
To the technical scheme in the embodiment of the present invention be clearly and completely described below, obviously, described embodiment is only a part of embodiment of the present invention, rather than whole embodiment.Based on the embodiment in the present invention, those of ordinary skills, not making all other embodiment that obtain under creative work prerequisite, belong to the scope of protection of the invention.
(1) cell culture and irradiation
H460 and H1299 cell are all purchased from Chinese Academy of Sciences's cell bank.Cell culture is in the RPMI 1640 containing high sugar, include 10% hyclone (Hyclone), 1 mM Sodium Pyruvate (Sigma-Aldrich company), 100 U/ ml penicillin-streptomycins (green skies biotechnology research institute) and 1 mM HEPES(pH7.2, Nanjing optically-active).24 h after cell inoculation, are changed to the fresh medium containing SB431542, and cultivate 1 h, then use RS2000 X-ray production apparatus (U.S.) to give the irradiation of various dose, and close rate is 1.16 Gy/min.According to rear different time point, collecting sample and analyzing.
(2) crystal violet measuring cell proliferation
Inoculating cell in 96 orifice plates, is changed to the fresh medium of the SB 431542 that contains variable concentrations after 24 hours.At i.e. 24, the 48 and 72 hours sucking-off culture fluid of different time points, wash twice with PBS, adding concentration is 0.5% crystal violet solution, at room temperature hatches after 15 minutes and cleans up and dry with tap water.Then, every hole adds the at room temperature jolting of sodium citrate/50% dehydrated alcohol 30 minutes that the pH value of 100 μ l 0.1 M is 4.2.At 540 nm places, read OD value by microplate reader (BIO-TEK POWERWAVE XS).
(3) colony formation
By radioactive dose, the cell of different densities is seeded in 60mm culture dish.After 24 hours, be changed to the 10 μ M fresh mediums that contain SB431542, after 1 hour, irradiate.After 14 days, the bacterium colony of formation is fixed with methanol, and used methylene blue staining.Number containing the colony that exceedes 50 cells is counted, and calculates the survival rate of cell.
(4) flow cytometry
H460 cell is seeded in 100 millimeters of culture dishs.After 24 hours, be changed to the 10 μ M fresh mediums that contain SB431542, after 1 hour, irradiate.After 5,24,48 or 72 hours, after collecting cell, be fixed in 70% ethanol, and be stored in-20 ℃ standby.Centrifuge cell suspension also washes twice with PBS, then is suspended in the 700 μ l propidium iodides (100 μ g/ml) containing the RNA enzyme of 0.1%NP40 and 500 μ g/ml, analyzes with flow cytometer (BECKMAN COULTER CYTOMICS FC500).Adopt the Multicycle AV for Windows analysis of cells cycle, CXP analysis analysis of cells apoptosis.
(5) immunofluorescence dyeing
By H460 cell kind on coverslip.After processing with distinct methods, in different time points, with 3.7% formaldehyde, cell is at room temperature fixed to 15 minutes.Wash away after residual fixative with PBS, with 0.5% ice-cold Triton-100 solution (containing 50 mM NaCl/3mM MgCl
2/ 200mM Sucrose/10mM HEPES, pH value are 7.4) at 4 ℃, hatch 15 minutes.With containing 5% lowlenthal serum and 0.2% skim milk confining liquid at room temperature sealed after 1 hour, hatch 45 or 90 minutes at room temperature or 37 ℃ respectively with 53BP1 or DNA-PKcs antibody (Abcam company), then use Alex Fluor
?anti-(1.5m g/ml) (Invitrogen company) of 488-conjugated goat anti-rabbit IgG bis-at room temperature lucifuge hatches 45 minutes.After PBS washed cell, with 4 ' of 10 μ g/ml, 6-diamidino-2-phenylindone (DAPI) dyeing 2 minutes, covers coverslip to have on the microscope slide in anti-quencher (the green skies) dripping, and at the lower counting of observing of fluorescence microscope (Leica DM2000).For the counting of 53BP1 foci, count the foci number in 100 cells; And for DNA-PKcs foci, the cell positive rate that meter contains foci, positive with the cell containing more than 10 or 10 foci.
(6) experiment in body
Nude mice (the female Mus of NC-nu 8 week age, average weight 23.0g) 3,000,000 H460 cells of left back inboard leg subcutaneous injection.When tumor reaches about 100mm
3after give packet transaction.20 tumor-bearing mices are divided into four groups at random, are respectively not processed group, simple dosing group, irradiation group merely, dosing and irradiation group, every group of 5 mices.Dosing group mice is accepted lumbar injection SB431542(10 mg/kg).After 2 h, the mice of dosing and irradiation group and simple irradiation group is carried out to the local irradiation (5 Gy) of tumor.After processing for three days on end, use vernier caliper measurement gross tumor volume every day, computing formula is for long × wide
2× 0.52.
(7) statistical analysis
In the present embodiment, all data that provide are the average of at least three independent experiments, and result is expressed as mean+/-standard error.Relatively employing OriginPro8 software between processed group and matched group carries out paired sample t check, and P value <0.05 is considered to have statistical significance.
(8) experimental result
1, the toxicity of SB 431542 to H460 cell:
Refer to Fig. 1 and Fig. 2, by analyzing variable concentrations SB431542, process the multiplication capacity of lower cell and verify the toxic action of SB431542 self to cell.10 μ M SB431542 do not have obvious inhibitory action to the propagation of H1299 cell in 72h, and 10 μ M SB431542 (24 or 48 h) do not affect the propagation of H460 cell yet in early days, but after processing, 72h can significantly reduce the multiplication capacity (20%) of H460 cell, and other low concentration is without statistical variations.Therefore SB 431542 concentration of, using in experiment are afterwards 10 μ M.
2, TGF-β 1 inhibitor SB431542 has increased H460 cell radiosensitivity:
Refer to Fig. 3 and Fig. 4, in colony formation, we make H1299 cell clonal formation rate reduce by 17% compared to matched group while finding 10 μ M SB431542 individual processing, and only make the cloning efficiency of H460 cell reduce by 6%.This is just contrary with the impact of its on cell proliferation.But SB431542 has increased the radiosensitivity of H460 cell, but inoperative to H1299 cell.Under 30% cloning efficiency, Dose Enhancement Ratio (DER) calculates as follows: for obtaining the dosage of 30% the required simple irradiation of cloning efficiency/under dosing condition for obtaining 30% the required radiation dose of cloning efficiency.For H1299 cell, its DER is 1.01, and the DER of H460 is 1.15.This shows that 10 μ M SB431542 have increased the radiosensitivity of H460 cell, but invalid to H1299 cell.
3, the rear H460 cell that changed of SB431542 inhibition TGF-β 1 is subject to the period profile after photograph, and apoptosis is not affected:
Refer to Fig. 5 and Fig. 6, in order to determine that SB431542 reduces H460 cell and is subject to the enhanced sensitivity mechanism according to rear multiplication capacity, we verified SB 431542 combine ray whether can change cell be subject to according to after period profile, and increase radiation-induced apoptosis.Following table be through SB431542 process or the H460 cell do not processed be subject to according to after cell cycle distribution, known SB431542 individual processing cell does not obviously change cell cycle distribution, but at SB 431542, combine under the Irradiation of 5 Gy dosage, compared with independent irradiation group, 24 h after processing, there is slight S phase cell block, and after 48 hours, cell has occurred that obvious G2/M phase blocks, illustrate that SB 431542 combines radiant energy and caused how residual DNA double chain interruption, thereby caused lasting cell cycle arrest.
Following table be through SB431542 process or the H460 cell do not processed be subject to according to after at different time points Sub-G1 shared percentage ratio in cell cycle, known not observing is subject to separately causing according to group and SB431542 associating radiation group the difference that has significance aspect apoptosis, shows that SB431542 is not to come from the promotion that cell is subject to the rear generation apoptosis of photograph to the radiation sensitizing effect of H460 cell.
4, SB431542 delayed H460 cell be subject to according to after DNA damage repair:
Through above-mentioned experiment, can clearly suppress the related mechanism that TGF-β 1 increases H460 cellular radiosensitivity, and explained more cell cycle arrest in SB435142 associating radiation group, studied as the 53BP1 foci of DNA double chain interruption labelling and be subject to the dynamic process according to rear appearing and subsiding at cell.Refer to Fig. 5 and Fig. 6, result shows, pre-irradiation has or not SB431542 to process the variation that does not cause the positive cell ratio that contains 53BP1 foci, but when we count the 53BP1 foci number in average each cell, but find and be subject to simple irradiating cell 30min after irradiation different to peaking, the pretreated cell of SB431542 is subject to according to rear 15min, 53BP1 foci number in its individual cells has arrived peak value, illustrates that SB431542 has accelerated cell and replied by the DNA damage after photograph.Although 1 h after irradiation, in the pretreated cell of SB431542, the number of residual 53BP1 foci is less than simple irradiating cell, but 4 h after irradiating, there is reverse in this trend, at least after irradiation within 8 h, in the pretreated cell of SB 431542, the number of residual 53BP1 foci is greater than simple irradiating cell, illustrates that SB 431542 combines DNA double chain interruption residual in the cell of radiation treatment more than simple irradiating cell.
For further clear and definite SB431542 pretreatment causes cell, be subject to the reason increasing according to rear residual DNA damage, whether we have studied again SB431542 pretreatment affects cell in the activation being subject to according to rear non-homogeneous end link path.Refer to Fig. 7 and Fig. 8, labelling using DNA-PKcs foci as non-homogeneous end link path, we find SB431542 pretreatment cause being subject to according to after contain DNA-PKcs foci positive cell rate at least within 1 h significantly lower than simple irradiating cell, and this species diversity of 6 h has disappeared after irradiation, this explanation SB431542 has weakened after cell exposure non-homogeneous end link repair ability in a short time.
5, SB431542 suppresses tumor growth in vivo:
Proved that SB431542 can increase the radiosensitivity of H460 cell in vitro, in the body of nude mice lotus tumor, experiment is whether to have synergism with radiation in vivo in order to study this inhibitor.Refer to Fig. 8,9 and 10, result shows, SB 431542 itself has the trend of tumor growth of reduction, this with experiment in vitro in, it is identical that SB431542 suppresses the propagation of H460 cell.The local irradiation of three continuous 5Gy has suppressed the growth of tumor significantly, and SB431542 combine be radiated at process after between the 5th day to the 12nd day, the volume of tumor has even occurred significantly to dwindle, and tumor is recovered growth afterwards, but the volume of tumor is still little compared with simple irradiation group.
Therefore, in order to verify, suppress TGF-β 1 possible sensitization in radiotherapy in lung cancer, we are clear and definite, and how TGF-β 1 inhibitor has changed the DNA damage reparation of cell and the radiosensitivity of non-small cell lung cancer cell.Data show, TGF-β 1 inhibitor SB 431541 can increase the radiosensitivity of H460 cell (wild type p53), and invalid to H1299 cell (mutant p53).The effect of H460 is shown as by changing cell cycle arrest, starting DNA damage fast and reply (DDR), but suppress the non-homogeneous end reparation of DNA double chain interruption, thereby reduce the cloning efficiency of cell.This enhanced sensitivity and apoptosis are irrelevant.Experiment also confirms compared with independent irradiation group in body, the x-ray bombardment processing that three SB 431542 add 5Gy make H460 transplanted tumor after processing in 5-15 days growth be subject to remarkable inhibition.
At pre-irradiation, with the kinase whose selective depressant SB431542 of TGF-β1receptor selectivity, suppress after TGF-β 1 path, p53 wild type H460 non-small cell lung cancer cell radiosensitivity increases, but invalid to p53 saltant type H1299 non-small cell lung cancer cell, illustrate that TGF-β 1 inhibitor is relevant with the p53 state of cell to the sensitization of lung carcinoma cell.In addition, the radiosensitizing effect of TGF-β 1 inhibitor to H460 cell and itself is irrelevant to the inhibition of cell clone rate, because SB431542 itself is greater than the inhibition to H460 to the inhibition of H1299 cloning efficiency.
The Mechanism Study that SB431542 is increased to the radiosensitivity of H460 cell shows, SB431542 pretreatment has been accelerated cell and has been subject to the DNA damage responsing reaction after photograph, the number that shows as 53BP1 foci arrives peaking according to rear 15 min rather than 30 min, and demonstration TGF-β 1 inhibition has been accelerated cell and has been subject to recruit the speed of albumen to injury site of repairing of identifying of damaging after DNA damage.But compared with simple irradiating cell, SB 431542 does not reduce the number of 53BP1 foci, illustrate that SB431542 is subject to the quantity of the DNA damage identification albumen that shines rear recruitment to reach the effect of radiation sensitivity by suppressing cell.But, although having started cell fast, SB 431542 is subject to the DNA damage responsing reaction after photograph, but to irradiating rear 4-8 h, in the cell of SB associating radiation treatment, the number of residual 53BP1 foci is but significantly higher than and is subject to merely photo cell, illustrates that pre-irradiation inhibition TGF-β 1 has reduced the ability of cytothesis DNA double chain interruption.Further studies show that, SB431542 has suppressed the formation of the DNA-PKcs foci at least 1 h after cell irradiation, illustrate that suppressing TGF-β 1 has reduced cell reparation to DNA damage by non-homogeneous end link path, this is also the reason of the how residual DNA damage of existence in the cell of SB431542 associating radiation treatment.And just because of there is how residual DNA damage, just cause the cell of SB associating radiation treatment different with simple cell cycle distribution of irradiating, exist more S phase and G2/M to block.It is not irrelevant mutually that these results suggest TGF-β 1 signal path and DNA damage are replied path, but can be interactional.The Radiosensitizing that suppresses TGF-β 1 path and increase H460 cell has nothing to do with apoptosis, shows that apoptosis does not work in to the sensitization of cell at SB431542.
In body, lotus tumor experiment showed, that, compared with blank group, the tumor growth of dosing group has the trend slowing down, and is subject at the 5th to 11 days, significantly to reduce with respect to the tumor of simple irradiation group according to dosing group.It may be that tumor propagation itself is accelerated again owing to processing not that both differences of later stage are dwindled.But, even like this, to compare with simple dosing group with matched group, the tumor of SB associating radiation group and tailored radiation group is still little a lot, shows that tumor has obtained effective control.
Therefore, in this research, we have confirmed that pre-irradiation suppresses TGF-β 1 and increase the radiosensitivity of p53 wild type nonsmall-cell lung cancer H460 cell, this support that we propose about the concept that suppresses TGF-β 1 signal and may improve radiotherapy in lung cancer curative effect.This radiosensitizing effect may be by changing DDR damage responsing reaction, suppressing the ability of non-homogeneous end DNA plerosis two strands and change cell cycle distribution to realize, irrelevant with apoptosis.But we are for SB 431542 as a kind of micromolecule reagent that suppresses TGF-β 1, the radiosensitivity that whether can increase other hypotype lung carcinoma cells is also very interesting.Because the tumor of most of types has mutant p53, so determine that the impact of the radiosensitivity of p53 state on inhibition TGF-β 1 rear increase tumor cell is most important.Study our well afoot for inferior.
The foregoing is only embodiments of the invention; not thereby limit the scope of the claims of the present invention; every equivalent structure or conversion of equivalent flow process that utilizes description of the present invention to do; or be directly or indirectly used in other relevant technical field, be all in like manner included in scope of patent protection of the present invention.
Claims (4)
1. the purposes of TGF-β 1 inhibitor in lung cancer therapy, is characterized in that, described TGF-β 1 inhibitor suppresses TGF-β 1 path increases the radiosensitivity of lung carcinoma cell.
2. the purposes of TGF-β 1 inhibitor according to claim 1 in lung cancer therapy, is characterized in that, described TGF-β 1 inhibitor is SB431542, and described lung carcinoma cell is p53 wild type Lines H460.
3. the purposes of TGF-β 1 inhibitor according to claim 1 in lung cancer therapy, is characterized in that, described TGF-β 1 inhibitor is relevant with the p53 state of lung carcinoma cell to the radiosensitivity effect of lung carcinoma cell.
4. the purposes of TGF-β 1 inhibitor according to claim 1 in lung cancer therapy, it is characterized in that, the effect of described TGF-β 1 inhibitor is by changing DDR damage responsing reaction, suppressing the ability of non-homogeneous end DNA plerosis two strands and change cell cycle distribution to realize.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410004597.7A CN103720689A (en) | 2014-01-06 | 2014-01-06 | Use of transforming growth factor (TGF)-beta1 inhibitor in lung cancer treatment |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410004597.7A CN103720689A (en) | 2014-01-06 | 2014-01-06 | Use of transforming growth factor (TGF)-beta1 inhibitor in lung cancer treatment |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103720689A true CN103720689A (en) | 2014-04-16 |
Family
ID=50445153
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410004597.7A Pending CN103720689A (en) | 2014-01-06 | 2014-01-06 | Use of transforming growth factor (TGF)-beta1 inhibitor in lung cancer treatment |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103720689A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106806894A (en) * | 2015-12-01 | 2017-06-09 | 海门雨霖细胞科技有限责任公司 | Small molecule compositions induction human tumor cells directly reprogram the method for non-tumorigenic cells |
| CN108449993A (en) * | 2015-08-19 | 2018-08-24 | 内奥利诊断公司 | The individual prediction technique of the DNA break genotoxicity effect of chemical reagent or biochemical reagents |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013013190A1 (en) * | 2011-07-21 | 2013-01-24 | The Regents Of The University Of California | Targeting gli proteins in human cancer by small molecules |
| CN103068970A (en) * | 2010-04-25 | 2013-04-24 | 西奈山医学院 | Generation of anterior foregut endoderm from pluripotent cells |
-
2014
- 2014-01-06 CN CN201410004597.7A patent/CN103720689A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103068970A (en) * | 2010-04-25 | 2013-04-24 | 西奈山医学院 | Generation of anterior foregut endoderm from pluripotent cells |
| WO2013013190A1 (en) * | 2011-07-21 | 2013-01-24 | The Regents Of The University Of California | Targeting gli proteins in human cancer by small molecules |
Non-Patent Citations (1)
| Title |
|---|
| YONG-CHUN ZHOU, ET AL.: "IONIZING RADIATION PROMOTES MIGRATION AND INVASION OF CANCER CELLS THROUGH TRANSFORMING GROWTH FACTOR-BETA–MEDIATED EPITHELIAL–MESENCHYMAL TRANSITION", 《INT. J. RADIATION ONCOLOGY BIOL. PHYS.》, vol. 81, no. 5, 31 December 2011 (2011-12-31), pages 1530 - 1537 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108449993A (en) * | 2015-08-19 | 2018-08-24 | 内奥利诊断公司 | The individual prediction technique of the DNA break genotoxicity effect of chemical reagent or biochemical reagents |
| CN106806894A (en) * | 2015-12-01 | 2017-06-09 | 海门雨霖细胞科技有限责任公司 | Small molecule compositions induction human tumor cells directly reprogram the method for non-tumorigenic cells |
| US10463641B2 (en) | 2015-12-01 | 2019-11-05 | Transcend Cytotherapy Co., Ltd | Method for using small molecule compounds to induce human tumor cells to be directly reprogrammed into non-oncogenic cells |
| CN106806894B (en) * | 2015-12-01 | 2021-06-25 | 海门雨霖细胞科技有限责任公司 | Method for inducing direct reprogramming of human tumor cells into non-tumorigenic cells by using small molecule composition |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Chaachouay et al. | Autophagy contributes to resistance of tumor cells to ionizing radiation | |
| Zhang et al. | Long non‐coding RNA ZEB2‐AS1 promotes the proliferation, metastasis and epithelial mesenchymal transition in triple‐negative breast cancer by epigenetically activating ZEB2 | |
| CN104363913B (en) | CDK8/CDK19 selective depressants and its purposes in the anti-rotation shifting of cancer and chemoprophylaxis method | |
| Sun et al. | Aurora-A controls cancer cell radio-and chemoresistance via ATM/Chk2-mediated DNA repair networks | |
| Kim et al. | NVP-BEZ-235 enhances radiosensitization via blockade of the PI3K/mTOR pathway in cisplatin-resistant non-small cell lung carcinoma | |
| Jiang et al. | Hypoxia potentiates the radiation-sensitizing effect of olaparib in human non-small cell lung cancer xenografts by contextual synthetic lethality | |
| Chen et al. | Cdc6 contributes to cisplatin-resistance by activation of ATR-Chk1 pathway in bladder cancer cells | |
| Wang et al. | PLK1 inhibition sensitizes breast cancer cells to radiation via suppressing autophagy | |
| Groselj et al. | Radiosensitisation of bladder cancer cells by panobinostat is modulated by Ku80 expression | |
| Chen et al. | MiR‐182 enhances radioresistance in non‐small cell lung cancer cells by regulating FOXO 3 | |
| Doghish et al. | miRNAs as potential game-changers in retinoblastoma: Future clinical and medicinal uses | |
| Hu et al. | The Protective Roles of ROS‐Mediated Mitophagy on 125I Seeds Radiation Induced Cell Death in HCT116 Cells | |
| Chen et al. | Adenosine A2A receptor activation reduces brain metastasis via SDF‐1/CXCR4 axis and protecting blood‐brain barrier | |
| Sun et al. | MicroRNA-574 enhances doxorubicin resistance through down-regulating SMAD4 in breast cancer cells. | |
| Zhu et al. | Retracted: MicroRNA‐198 inhibition of HGF/c‐MET signaling pathway overcomes resistance to radiotherapy and induces apoptosis in human non–small‐cell lung cancer | |
| Zhang et al. | Icotinib enhances lung cancer cell radiosensitivity in vitro and in vivo by inhibiting MAPK/ERK and AKT activation | |
| Girard et al. | Heterogeneity of chondrosarcomas response to irradiations with X-rays and carbon ions: A comparative study on five cell lines | |
| Liao et al. | HIF-1α siRNA and cisplatin in combination suppresstumor growth in a nude mice model of esophageal squamous cell carcinoma | |
| CN103720689A (en) | Use of transforming growth factor (TGF)-beta1 inhibitor in lung cancer treatment | |
| US10087448B2 (en) | Synthetic lethality in cancer | |
| Wang | LncRNA CCAT1 downregulation increases the radiosensitivity of non‐small cell lung cancer cells | |
| Gao et al. | Radiosensitization of HT‐29 cells and xenografts by the nitric oxide donor DETANONOate | |
| Altmeyer et al. | Pharmacological enhancement of autophagy induced in a hepatocellular carcinoma cell line by high-LET radiation | |
| Li et al. | Long noncoding RNA ARSR is associated with a poor prognosis in patients with colorectal cancer | |
| CN102028957A (en) | Application of BTG2 (B cell translocation gene 2) in preparing radiation sensitizing agent |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20140416 |