CN102499942A - Application of combined utilization of triptolide cisplatin in preparation of pancreatic cancer drug against drug resistance - Google Patents
Application of combined utilization of triptolide cisplatin in preparation of pancreatic cancer drug against drug resistance Download PDFInfo
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- CN102499942A CN102499942A CN2011103845059A CN201110384505A CN102499942A CN 102499942 A CN102499942 A CN 102499942A CN 2011103845059 A CN2011103845059 A CN 2011103845059A CN 201110384505 A CN201110384505 A CN 201110384505A CN 102499942 A CN102499942 A CN 102499942A
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Abstract
The invention discloses an application of combined utilization of triptolide cisplatin in preparation of a pancreatic cancer drug against drug resistance. Experiments on two drug-resistant pancreatic cancer cells PANC-1 and MIAPaCa-2 and nude mice with inoculated with PANC-1 cells on flanks prove that the effects of synergistic tumor inhibition can be achieved for drug-resistant pancreatic cancer through the combined utilization of triptolide cisplatin. So far, no study on the synergistic inhibition of the pancreatic cancer through the combined utilization of triptolide cisplatin is reported. In the nude mouse xenografting model, the tumor growth can be significantly inhibited through the combined utilization of low doses of triptolide and cisplatin, and cannot be inhibited when only the triptolide or cisplatin is used. The results of immunohistochemistry for each group of tumor biopsies show that the HSP27 protein expression can be reduced significantly through the combined utilization of the two drugs, and the results are identical to the results on cell lines. Therefore, the triptolide and cisplatin can be used together as a sensitizing agent of anticancer drugs.
Description
Technical field
The present invention relates to cisplatin combined being used in of triptolide and prepare anti-drug resistance cancer of pancreas medicine and the application in preparation antitumor drug sensitizer.
Background technology
Cancer of pancreas is a kind of common digestive tract tumor, has grade malignancy height, invasion and attack speed is fast and fatality rate is high characteristics.Owing to still lack the effective means of early discovery cancer of pancreas at present, to make a definite diagnosis the back disease progression rapid in addition, causes most pancreatic adenocarcinoma patient can't implement operation.According to the latest estimated (GLOBOCAN 2008) of DKFZ of World Health Organization (WHO), annual new diagnosis of pancreatic carninomatosis example 27.87 ten thousand examples in the global range, dead 26.27 examples, dead morbidity is than being 0.94 [1].In all common malignancy, the survival rate of Pancreas cancer patients is minimum, and its average median survival interval is 3 months, and 5 years survival rates are 3-5%.List of references [1].[1]?Ferlay?J,?Shin?HR,?Bray?F,?et?al.?GLOBOCAN?2008,?Cancer?Incidence?and?Mortality?Worldwide:?IARC?CancerBase?No.10.http://www.iarc.fr/en/publication/eresources/cancerbases/index.php
The pyrimidine nucleoside analoys gemcitabine has been considered to treat the unique effective medicine of cancer of pancreas since last century end, but the patient who also has only 20-30% is to this susceptibility sense, and this medicine and other line cancer therapy drug are united utilization and do not seen synergism [2-4].The generation of the toleration of medicine is the main reason that causes cancer of pancreas chemotherapy failure.Become an important directions of treatment cancer of pancreas to the new chemotherapeutic agent of drug resistance sexual development.List of references [2-4].[2]?Ina?S,?Hirono?S,?Noda?T,?et?al.?Identifying?molecular?markers?for?chemosensitivity?to?gemcitabine?in?pancreatic?cancer:?increased?expression?of?interferon-stimulated?gene?15?kd?is?associated?with?intrinsic?chemoresistance
.Pancreas.?39(4):?473-485. [3] Rivera?F,?Lopez-Tarruella?S,?Vega-Villegas?ME,?et?al.?Treatment?of?advanced?pancreatic?cancer:?from?gemcitabine?single?agent?to?combinations?and?targeted?therapy
.Cancer?Treat?Rev.?2009.?35(4):?335-339. [4]?Heinemann?V.?Gemcitabine:?progress?in?the?treatment?of?pancreatic?cancer
.Oncology.?2001.?60(1):?8-18.
Triptolide is from Celastraceae plant Radix Tripterygii Wilfordii
Tripterygium wilfoudii Hook. f. kThe middle epoxidation diterpenic lactone that obtains that separates.Radix Tripterygii Wilfordii is used to treat autoimmune disease such as nephritis, rheumatoid arthritis etc. have had several centuries.In recent years, get more and more and discover that triptolide has very strong active anticancer, through promoting that apoptosis of tumor cells significantly suppresses growth of tumor and transfer.Triptolide and multiple anticarcinogen (like cytosine arabinoside, amycin, topoisomerase I inhibitor C PT-11) are united the antitumous effect that utilization can strengthen these medicines, and the prompting triptolide is as the application potential [5,6] of tumor sensitizer.List of references [5] and [6].[5]?Pigneux?A,?Mahon?FX,?Uhalde?M,?et?al.?TPL?cooperates?with?chemotherapy?to?induce?apoptosis?in?acute?myeloid?leukemia?cells.?
Exp?Hematol.?2008.?36(12):?1648-1659.?[6]?Chang?WT,?Kang?JJ,?Lee?KY,?et?al.?TPL?and?chemotherapy?cooperate?in?tumor?cell?apoptosis.?A?role?for?the?p53?pathway.
?J?Biol?Chem.?2001.?276(3):?2221-2227.
Cisplatin belongs to the high-efficiency broad spectrum anticarcinogen, mainly suppresses tumor growth through cell death inducing.It is insensitive to treatment of pancreatic cancer, unites utilization with gemcitabine and does not also reach ideal therapeutical effect [7].List of references [7].[7]?Choi?JH,?Oh?SY,?Kwon?HC,?et?al.?Gemcitabine?versus?gemcitabine?combined?with?DDP?treatment?locally?advanced?or?metastatic?pancreatic?cancer:?a?retrospective?analysis
.Cancer?Res?Treat.?2008.?40(1):?22-26.
HSP27 comprises HSP79, and HSP90 all is heat shock protein man HSPs members of family.HSPs belongs to a kind of of stress protein.As micromolecule bridesmaid albumen, HPSs participates in apoptosis process and canceration process.A large amount of bibliographical information HSP27 expresses such as gastric cancer, colon cancer, ovarian cancer and lymphatic cancer camber in the tumor of drug resistance, in drug resistance, has played the part of important effect.At pernicious pancreas cancer cell strain of aggressive and the insensitive cell strain of androgen, HSP27 expresses significantly and raises.HSP27 possibly be a potential target spot [8] to Drug tolerance.List of references [8].[8]?Cornford?PA,?Dodson?AR,?Parsons?KF,?et?al.?Heat?shock?protein?expression?independently?predicts?clinical?outcome?in?prostate?cancer
.Cancer?Res.?2000.?60(24):?7099-7105.
We discover, with independent utilization triptolide with compare with cisplatin, triptolide and cisplatin combined utilization can be worked in coordination with enhancing to drug resistance cancer of pancreas PANC-1 and the effect of MIA PaCa-2 induced apoptosis.The test of nude mice heterotopic transplantation tumor shows that triptolide and cisplatin combined utilization have significantly strengthened tumor-suppression activity.According to our literature search, do not see report so far about triptolide and or tumor killing effect anticancer with the collaborative enhancing of cisplatin combined utilization.
Summary of the invention
The objective of the invention is to overcome the deficiency of prior art, a kind of pharmaceutical composition is provided, said composition is made up of triptolide and cisplatin.
Another object of the present invention provides the application of above-mentioned composition in preparation anti-drug resistance cancer of pancreas medicine.
Further purpose of the present invention provides the application of above-mentioned composition in preparation antitumor drug sensitizer.
To achieve these goals, the present invention adopts following technical scheme:
Our research shows, in drug resistance pancreas cancer cell strain PANC-1 and MIA PaCa-2, utilization only slightly reduces the cells survival rate than the triptolide or the cisplatin of low dosage separately, and that The combined has reduced survival rate is about more than 50%.Simultaneously, measure the therapeutic alliance coefficient CI that obtains through both a plurality of concentration Combined application and be lower than 1, show two kinds of medicines
But the Synergistic killing pancreatic cancer cell, its collaborative tumor-inhibiting action is realized through line graininess approach.Triptolide and cisplatin ratio of weight and number are 1-20:2-120.The collaborative cancer suppressing action of triptolide-cisplatin possibly significantly reduced with HSP27 and be closely related.In addition, concentrate, cracked nucleus resembles and apoptosis to carry out active 3.3 multiplications of enzyme caspase-3 strong, further point out two kinds of medication combined application to induce tangible apoptosis, and effect is obvious separately.
Triptolide-cisplatin combined utilization; Use triptolide or cisplatin more separately; The content of cytochrome C and Caspase-9 are active in the PANC-1 cytoplasm significantly increases, and shows that triptolide-cisplatin co-induction apoptotic effect mediates through line grain approach.
Compare with independent application triptolide or cisplatin, The combined is used to work in coordination with the HSP27 downward modulation is expressed.Reticent HSP27 gene can make the PANC-1 cell that the sensitivity of triptolide or cisplatin is improved, and survival rate is single obviously to be reduced with chemotherapeutics.The anticancer effect of these promptings HSP27 downward modulation can enhancing medicine maybe be relevant with cisplatin combined utilization enhancing chemotherapy sensitivity with triptolide.
On the bare mouse different species transplantation model; Unite triptolide (0.25 mg/kg that uses low dosage; 1 time/2 days) and cisplatin (3mg/kg, 1 time/1 week) significantly suppress growth of tumor, and single can not cause all that with triptolide or cisplatin growth of tumor suppresses.SABC result to the tumor biopsy of each group shows that two kinds of drug combinations are significantly reduced the protein expression of HSP27, and is consistent with result on the cell strain.This explanation triptolide and cisplatin combined utilization can be as the sensitizers of antitumor drug.
To sum up, triptolide-cisplatin combined utilization has the obvious synergistic inhibitory action to the drug resistance cancer of pancreas.Up to the present, also do not have the collaborative research report that suppresses cancer of pancreas about triptolide-cisplatin combined utilization.
Description of drawings
Fig. 1 has strengthened the pancreas cancer cell strain PANC-1 apoptosis induced effect of cisplatin to the gemcitabine tolerance for triptolide.
The influence of A triptolide pair cell survival rate; B Hoechst 33258 dyeing: arrow refers to the nucleus of apoptotic cell; The activity of C caspase-3; The relative burst size of D lactic acid dehydrogenase (LDH).Numerical value is with mean+SD (n=3).PANC-1 through triptolide (25 nM) and (or) cisplatin (16 μ M) incubated 48 hours altogether; TPL-triptolide; DDP-cisplatin; TPL+DDP-triptolide and cisplatin combined utilization; Compare * with matched group
p<0.05, * *
P<0.01.
Fig. 2 has strengthened the pancreas cancer cell strain MIA PaCa-2 apoptosis induced effect of cisplatin to the gemcitabine tolerance for triptolide.
The influence of A triptolide pair cell survival rate; B Hoechst 33258 dyeing arrows refer to the nucleus of apoptotic cell; The activity of C caspase-3; The relative burst size of D lactic acid dehydrogenase (LDH).Numerical value is with mean+SD (n=3).MIA PaCa-2 through triptolide (25 nM) and (or) cisplatin (16 μ M) incubated 48 hours altogether; TPL-triptolide; DDP-cisplatin; TPL+DDP-triptolide and cisplatin combined utilization; Compare * with matched group
p<0.05, * *
P<0.01.
Fig. 3 is that the synergism of triptolide and cisplatin induction apoptosis mediates through the mitochondrion approach.
The relative release of A Cytochrome c; B caspase-9 is active.PANC-1 through triptolide (25 nM) and (or) cisplatin (16 μ M) incubated 48 hours altogether; TPL-triptolide; DDP-cisplatin; TPL+DDP-triptolide and cisplatin combined utilization; Compare * * with matched group
P<0.01.
Fig. 4 has reduced the protein expression of HSP27 in the PANC-1 cell for triptolide and cisplatin combined utilization.
The A triptolide is to the influence of HSP27, HSP70, HSP90 protein level; The B cisplatin is to the influence of HSP27, HSP70, HSP90 protein level; C triptolide and cisplatin combined utilization are to the influence of HSP27 and HSP70 protein level.PANC-1 through triptolide (25 nM) and (or) cisplatin (16 μ M) incubated 48 hours altogether; TPL-triptolide; DDP-cisplatin; TPL+DDP-triptolide and cisplatin combined utilization; Compare * * or ## p < 0.01 with matched group.
Fig. 5 has strengthened triptolide or the cisplatin lethal effect to the PANC-1 cell for HSP27 knocks out.
The silence of A HSP27: concentration is that siRNA fragment 01,02 and 03 pair of PANC-1 cell of 50 nM intervened 48 hours reticent effectiveness detection; The reticent HSP27 of B is to the sensitization of triptolide killing tumor cell; The reticent HSP27 of C is to the sensitization of cisplatin killing tumor cell.P < compare with HSP27-siRNA associating triptolide group by 0.05 negative control oligonucleotide associating triptolide; P 0.01 negative control oligonucleotide combination with cisplatin is compared with HSP27-siRNA combination with cisplatin group.
Fig. 6 has suppressed growth of tumor significantly for triptolide and cisplatin combined utilization.
The A Drug therapy is to the influence of nude mice heteroplastic transplantation growth of tumor: PANC-1 cell (5 * 10
6) be inoculated into 6 the week age nude mice flank.After 10 days; The nude mice that has successfully inoculated tumor is divided into four groups, contains normal saline (1 time/2 days), triptolide 0.25 mg/kg (1 time/2 days), the cisplatin 3mg/kg (1 time/1 week) of 1% DMSO respectively and unite to give triptolide and cisplatin.
p<0.01, compare with group of solvents; The tumor weight of the 25th day animal of B; The form size of C tumor; The body weight change of D nude mice; The HSP27 protein level that E measures through the SABC method.Vehicle-group of solvents; TP-triptolide group; DDP-cisplatin group; TPL+DDP-triptolide and cisplatin combined utilization group.
The specific embodiment
Embodiment 1 triptolide strengthens the pancreas cancer cell strain PANC-1 apoptosis induced effect of cisplatin to the gemcitabine tolerance
1) mensuration of cell survival rate
Tumor cell is with the DMEM culture medium dilution that contains 10% (v/v) FBS and be seeded to 96 orifice plates.Making cell concentration is 2 * 10
3/ hole, 37 ℃, 5%CO
2Incubated overnight.Then add medicine, hatched 48 hours.Every then hole adds 20 ul MTT solution, continues to cultivate 4 h.The centrifugal 10min of 1000rpm carefully sops up supernatant, and every hole adds 100 ul dimethyl sulfoxide, puts low-speed oscillation 10 min on the shaking table, and crystal is fully dissolved.Locate to measure the light absorption value OD in each hole in 570nm (630nm calibration) at enzyme-linked immunosorbent assay instrument.
Cell survival rate=OD
t/ OD
c* 100%
OD
t, test group OD value; OD
c, matched group OD value.
2) caspase-3 determination of activity
With tumor cell (2 * 10
6/ hole) be seeded to 6 orifice plates, overnight incubation makes adherent.Add medicine, hatched 48 hours.Ice bath adds lysate cracking 15 min down, and 4 ℃ of centrifugal 10 min of 15000rpm draw supernatant and measure upward albumin content with the Lowry method.Add reaction buffer and caspase-3 substrate, cultivated 4 hours, measure the OD value at 405 nm places with ELIASA.With protein content the caspase-3 activity is carried out standardization, the result is expressed as the relative ratio with matched group.
3) Hoechst 33342 dyeing
Add Hoechst 33342 in the tumor cell, lucifuge is cultivated 20min, with PBS washing 2-3 time, observes under fluorescence microscope in 340 nm.
4) the LDH burst size detects
With tumor cell (2 * 10
6/ hole) be seeded to 6 orifice plates, overnight incubation makes adherent.Add medicine, hatched 48 hours.50 μ l supernatant of culture medium are drawn in another 96 orifice plate in every hole, and every hole adds reactant liquor 50 μ l, puts 37 ℃ of 5% CO
2CO2 gas incubator in cultivate 30 min.Add 50 μ l stop buffers then, on ELIASA, measure the OD value in each hole with wavelength 450 nm.The result is expressed as the relative ratio with matched group.
In the pancreas cancer cell strain PANC-1 of gemcitabine tolerance; Use triptolide (TPL separately; 25 nM) or cisplatin (DDP; 16 μ M) only reduced the survival rate of PANC-1 cell slightly, two kinds of medication combined utilizations (TPL+DDP) then reduced significantly cell survival rate (with matched group relatively, reduced by 54%).Therapeutic alliance coefficient CI is lower than 1, and disclosing two kinds of medication combined utilizations is synergism.Cell carries out morphological observation after Hoechst 33342 dyeing, compare with other group, and obviously concentrating with cracked appears in drug combination group nucleus.Medication combined utilization group, the activity of the caspase-3 that in apoptosis, plays an important role is compared than matched group, has strengthened 3.3 times.By contrast, the triptolide group has only strengthened 1.46 times, and cisplatin is 1.87 times.Each is organized LDH and discharges to compare with matched group and all do not see obvious change.The result is as shown in Figure 1.
Cell survival rate, caspase-3 activity, Hoechst 33342 dyeing and LDH discharge with embodiment 1.
In the pancreatic cancer cell MIA PaCa-2 of gemcitabine tolerance; Use triptolide (TPL separately; 25 nM) or cisplatin (DDP; 16 μ M) only reduced cell survival rate slightly, two kinds of medication combined utilizations (TPL+DDP) have then reduced cell survival rate (compare with matched group, reduced by 59 %) significantly.Therapeutic alliance coefficient CI is lower than 1, and disclosing two kinds of medication combined utilizations is synergism.Cell carries out morphological observation after Hoechst 33342 dyeing, compare with other group, and obviously concentrating with cracked appears in drug combination group nucleus.Medication combined utilization group, the activity of the caspase-3 that in apoptosis, plays an important role has strengthened 2.6 times than matched group.By contrast, the triptolide group has only strengthened 1.25 times, and cisplatin is 1.65 times.Each is organized LDH and discharges to compare with matched group and all do not see obvious change.The result is as shown in Figure 2.
1) cytochrome C is measured
With tumor cell ((2 * 10
6/ hole) be seeded to 6 orifice plates, overnight incubation makes adherent.Add medicine, hatched 48 hours.The plasmosin of each group of extracting, plasmosin liquid and the cytochrome C titer behind the gradient dilution that will test each group again add 96 hole ELISA Plates, and every hole 100 μ l spend the night.Each sample adds 3 holes, to identify the false positive results due to distinguishing positive findings and polluting.Next day, with the culture fluid sucking-off in 96 orifice plates, operate by EL I SA test kit step: (w ash solution) washes 1 time with washing liquid, adds analytic liquid (assay diluent), every hole 200 μ l room temperature 1h.Adding is shaken 3 h with (1:350) mouse-anti horse cytochrome C antibody of analytic liquid dilution under the room temperature.After washing 3 times with washing liquid, add two anti-with the anti-human IgG of (1:1000) HRP labelling of analytic liquid dilution, shake 1h under the room temperature.Add photosensitizer after washing 8 times, cessation reaction behind the 30m in, reading under ELIASA 450nm.With protein content the caspase-3 activity is carried out standardization, the result is expressed as the relative ratio with matched group.The result is shown in Fig. 3 A.
2) caspase-9 determination of activity
Measure with the luminous experiment of Caspase-GloTM.Cell ((2 * 10
5/ hole) be seeded in simultaneously in transparent and opaque 96 orifice plates, overnight incubation makes adherent.Add 100 μ l Caspase-Glo reactant liquors, jolting makes mixing gently, hatches under the room temperature after 1.5 hours to measure fluorescent.Transparent 96 orifice plates are measured cell survival rate with the MMT method.With cell number the caspase-9 activity is carried out standardization, the result is expressed as the relative ratio with matched group.
In the PANC-1 cell, triptolide-cisplatin combined utilization has significantly strengthened cytochrome C and has discharged into the amount of cytosol from mitochondrion, compares with matched group, and the content of cytochrome C raise about 3 times.Triptolide-cisplatin combined utilization, Caspase-9 activity are compared with matched group has increased about 9 times.All use triptolide or cisplatin that remarkable rising is arranged more separately.Prompting, the collaborative tumor-inhibiting action of triptolide-cisplatin mediates through line grain approach.The result is shown in Fig. 3 B.
The protein expression of HSP27 in the PANC-1 cell has been reduced in embodiment 4 triptolides and cisplatin combined utilization
Western blotting carries out with reference to the method for reports such as Qiu [9].As shown in Figure 4, but triptolide is applied in the protein expression of the reduction HSP27 of dose dependent in 25nM to the 100nM concentration range separately, and 100nM can reduce the expression of HSP70, and HSP90 is not had influence; Cisplatin uses the not influence of protein expression to HSP70 and HSP90 separately, but the protein expression of the downward modulation HSP27 of ability dose dependent.With the increase of triptolide and cisplatin concentration, the HSP27 protein expression is concentration and relies on the ground downward modulation.With the cisplatin combined utilization of 25nM triptolide and 16 μ M, HSP27 is lowered to a quite low level.HSP27 can suppress apoptosis through combining cytochrome c, and therefore this proteic collaborative downward modulation is likely the important mechanism of triptolide and cisplatin combined utilization co-induction apoptosis.List of references [9].[9]?Qiu?D,?Zhao?G,?Aoki?Y,?et?al.?Immunosuppressant?PG490?(TPL)?inhibits?T-cell?interleukin-2?expression?at?the?level?of?purine-box/nuclear?factor?of?activated?T-cells?and?NF-kappaB?transcriptional?activation
.J?Biol?Chem.?1999.?274(19):?13443-13450.
Take three pairs to disturb segment SiRNA001, SiRNA002, SiRNA003 knocks out the HSP27 gene.As shown in Figure 5, confirm that through Western blotting SiRNA 03 is that HSP27 the most effectively disturbs segment.Compare with the positive control oligonucleotide, reticent HSP27 gene obviously strengthens the triptolide of each dosage or the lethal effect of cisplatin pair cell.Prompting HSP27 downward modulation can strengthen the sensitivity of pancreatic cancer cell to triptolide or cisplatin, possibly be triptolide and the enhanced major reason of cisplatin combined utilization chemotherapy sensitivity.
Embodiment 6 triptolides and cisplatin combined utilization have suppressed growth of tumor significantly
PANC-1 cell (5 * 10
6) be inoculated into 6 age in week nude mice flank subcutaneous.After 4 days; The nude mice that has successfully inoculated the dystopy tumor is divided into four groups, contains normal saline (1 time/2 days), triptolide 0.25 mg/kg (1 time/2 days), the cisplatin 3mg/kg (1 time/1 week) of 1% DMSO respectively and unite and give triptolide and cisplatin.After 25 days, put to death nude mice, tumor resection is measured the tumor size.
Tumor tissues is fixed 24 hours with 4% formalin buffer, use FFPE.Carry out heat fixation, remove deparaffnize and again after the aquation, tissue slice is immersed 10mM citrate buffer solution (pH 6.0) microwave 10min.Tissue slice and 1.5% block serum cultivated 1 hour, then with 4 ℃ of incubated overnight of HSP27 antibody.In conjunction with the SA 1 hour of HPR.At last, tissue slice is redyed with Gills Hemtoxylin III, under inverted microscope, observes.
On the bare mouse different species transplantation model, use the triptolide or the cisplatin of low dosage separately, to the inhibitory action of tumor growth not statistically significant.Yet, unite the triptolide and the cisplatin that use low dosage and significantly reduced tumor size and quality.SABC is the result also show, the medication combined HSP27 that reduced.The result is as shown in Figure 6.
Claims (3)
1. a compositions is characterized in that, is made up of triptolide and cisplatin, and triptolide and cisplatin ratio of weight and number are 1-20:2-120.
2. the application of the said compositions of claim 1 in preparation anti-drug resistance cancer of pancreas medicine.
3. the application of the said compositions of claim 1 in preparation antitumor drug sensitizer.
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Cited By (5)
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| CN103656646A (en) * | 2013-12-22 | 2014-03-26 | 王雪雁 | Anti-tumor drug composition and application thereof |
| CN105362290A (en) * | 2015-12-11 | 2016-03-02 | 济南鲁拓生物制药有限公司 | Novel triptolide anti-cancer drug |
| CN107041875A (en) * | 2017-02-28 | 2017-08-15 | 嘉兴学院 | Silk-fibroin nanoparticle and its application |
| CN107320486A (en) * | 2016-04-28 | 2017-11-07 | 南京大学 | Application of the andrographolide with cisplatin combined medication in treatment cisplatin-resistant lung-cancer medicament is prepared |
| CN114796238A (en) * | 2022-03-30 | 2022-07-29 | 华侨大学 | Tripterygium wilfordii composition for inhibiting drug-resistant cancer and preparation method and application thereof |
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2011
- 2011-11-28 CN CN2011103845059A patent/CN102499942A/en active Pending
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103656646A (en) * | 2013-12-22 | 2014-03-26 | 王雪雁 | Anti-tumor drug composition and application thereof |
| CN105362290A (en) * | 2015-12-11 | 2016-03-02 | 济南鲁拓生物制药有限公司 | Novel triptolide anti-cancer drug |
| CN107320486A (en) * | 2016-04-28 | 2017-11-07 | 南京大学 | Application of the andrographolide with cisplatin combined medication in treatment cisplatin-resistant lung-cancer medicament is prepared |
| CN107041875A (en) * | 2017-02-28 | 2017-08-15 | 嘉兴学院 | Silk-fibroin nanoparticle and its application |
| CN107041875B (en) * | 2017-02-28 | 2019-12-13 | 嘉兴学院 | Fibroin nanoparticles and application thereof |
| CN114796238A (en) * | 2022-03-30 | 2022-07-29 | 华侨大学 | Tripterygium wilfordii composition for inhibiting drug-resistant cancer and preparation method and application thereof |
| CN114796238B (en) * | 2022-03-30 | 2023-04-28 | 华侨大学 | Tripterygium wilfordii composition for inhibiting drug-resistant cancers and preparation method and application thereof |
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