CN108309990A - Triptonide is used to prepare Gli gene inhibitors and prevents the biomedical uses of liver-cancer medicine - Google Patents
Triptonide is used to prepare Gli gene inhibitors and prevents the biomedical uses of liver-cancer medicine Download PDFInfo
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Abstract
It is used to prepare Gli gene inhibitors the invention discloses triptonide and prevents the biomedical uses of liver-cancer medicine.Present invention discover that, triptonide can be by inhibiting Gli1, Gli2 gene expression to significantly inhibit the proliferation of liver cancer cells, and apparent dose dependent is presented in inhibiting effect, effective inhibitor of triptonide Gli1, Gli2 gene can be used for preparing the drug of prevention liver cancer.One skilled in the art will appreciate that it is a kind of more mature anti-cancer molecules access to inhibit Gli1, Gli2 gene expression, triptonide is exactly based on this access and plays antihepatocarcinoma effect.Simultaneously as triptonide is effective inhibitor of Gli1, Gli2 gene expression, triptonide can be used for preparing the drug of the treatment relevant disease of Gli1, Gli2 gene high expression.
Description
Technical field
The invention belongs to biomedicine fields, are related to the new application of known compound, and in particular to triptonide is used
In the biomedical uses for preparing Gli gene inhibitors and prevention liver-cancer medicine.
Background technology
Triptonide is a kind of natural products isolated from tripterygium wilfordii, and chemical structural formula is as follows：
Some researches show that triptonide can reduce the expression for the non-coding RNA for promoting cancer in stomach cancer cell, make its evil
Sexual behaviour is significantly inhibited, and has good application value (bibliography in the treatment of gastric cancer：Triptonide inhibits
The effect of stomach cancer cell malignant activity and mechanism study, traditional Chinese medicine are notified to the 5th phases of volume 16 in 2017).
Not yet find triptonide in the report for preventing liver cancer at present.Change of the project team in screening treatment liver cancer
It is found when closing object, triptonide has excellent resisting liver cancer activity, and specifies its anti-cancer molecules mechanism.
Invention content
The first object of the present invention is to provide the use that triptonide is used to prepare Gli1, Gli2 gene inhibitor
On the way；
The second object of the present invention is to provide the purposes that triptonide is used to prepare prevention liver-cancer medicine；
The third object of the present invention is to provide the pharmaceutical preparation of triptonide.
The above-mentioned purpose of the present invention is achieved by following technical solution：
Triptonide is used as the biomedical uses of Gli1 gene expression inhibitors.
Triptonide is used as the biomedical uses of Gli2 gene expression inhibitors.
Triptonide is used as preparing the biomedical uses of the drug of prevention liver cancer.
A kind of pharmaceutical preparation, including active constituent triptonide or its pharmaceutical salts further include that can pharmaceutically receive
Carrier or excipient, pharmaceutically acceptable dosage form is made.
Preferably, the pharmaceutically acceptable carrier or excipient include one or more solids, semisolid or liquid
Body auxiliary material.
Preferably, the pharmaceutically acceptable dosage form includes tablet, capsule, granule, injection, pill, sugar
Starch agent, powder, paste etc..
Advantages of the present invention：
It is a discovery of the invention that triptonide can be by inhibiting Gli1, Gli2 gene expression to significantly inhibit liver cancer cells
Proliferation, and apparent dose dependent, effective inhibition of triptonide Gli1, Gli2 gene is presented in inhibiting effect
Agent can be used for preparing the drug of prevention liver cancer.One skilled in the art will appreciate that it is a kind of to inhibit Gli1, Gli2 gene expression
More mature anti-cancer molecules access, triptonide are exactly based on this access and play antihepatocarcinoma effect.Simultaneously as thunder
Public rattan lactone ketone be Gli1, Gli2 gene expression effective inhibitor, triptonide can be used for prepare treatment Gli1,
The drug of the relevant disease of Gli2 gene high expressions.
Description of the drawings
Fig. 1 is proliferation inhibition rate of the basic, normal, high dosage of triptonide to HepG2, SMMC-7721 cell；
Fig. 2 is the relative expression quantity of Gli1mRNA, Gli2mRNA in each administration group HepG2, SMMC-7721 cell；
Fig. 3 is the relative expression quantity of Gli1 albumen, Gli2 albumen in each administration group HepG2, SMMC-7721 cell.
Specific implementation mode
It is specific with reference to the accompanying drawings and examples to introduce essentiality content of the present invention, but the guarantor of the present invention is not limited with this
Protect range.
Embodiment 1：The influence that triptonide is proliferated human hepatoma HepG2 cell
One, experiment material
Human hepatoma HepG2 cell's strain is purchased from Shanghai Ji Kai gene technology Co., Ltd；
DMEM culture mediums, fetal calf serum and PBS are purchased from Gibco companies；TRIzol is purchased from Invitrogen companies；Reverse transcription
Kit is purchased from Fermentas companies of the U.S., and PCR kit for fluorescence quantitative is purchased from TaKaRa treasured bioengineering (Dalian) limited public affairs
Department；Cell pyrolysis liquid, SDS-PAGE albumen sample-loading buffer (5 ×), BCA albumen concentration determinations kit, 20 × TPBS bufferings
Liquid etc. is purchased from the green skies biotechnology research institute in Jiangsu, and pvdf membrane is purchased from Millipore companies of the U.S.；CCK-8 kits are purchased from
Japanese colleague's chemistry institute；Gli1, Gli2 and GAPDH primer are synthesized by Shanghai Sheng Gong bio-engineering corporations；
Rabbit-anti people Gli1 monoclonal antibodies, rabbit-anti people's Gli2 monoclonal antibodies are purchased from U.S. Santa Cruz
Biotechnology, the anti-human GAPDH monoclonal antibodies of mouse are purchased from Beijing Bioisystech Co., Ltd of Zhong Shan Golden Bridge.
Two, experimental method
1, human hepatoma HepG2 cell cultivates
HepG2 cell lines are in 37 DEG C, 5%CO2, under the conditions of saturated humidity, be placed in containing 10% fetal calf serum,
Secondary culture in the DMEM culture mediums of 100U/mL penicillin and 100U/mL streptomysins passes on 1 time per 2d, and logarithmic growth phase is thin
Born of the same parents.
2, experiment packet
Triptonide low dosage administration group (7.5 μM)；
Triptonide middle dosage administration group (15 μM)；
Triptonide high dose administration group (30 μM)；
Control group：HepG2 cells without any drug-treated.
3, CCK-8 methods measure cell proliferation inhibition rate
It is with reference to kit specification, the HepG2 of exponential phase is cells trypsinised, centrifugation, with containing 10%
The DMEM culture mediums of fetal calf serum are made into cell suspension, and being seeded to 96 orifice plates makes cell density be 5 × 104/ mL is wet being saturated
Degree, 37 DEG C, 5%CO2Under conditions of cultivate and make cell adherent for 24 hours.By whole mass concentration dosing needed for above-mentioned grouping, control group is only
Add the PBS of pH7.4, each mass concentration that 6 multiple holes are set, CCK-8 48h after processing are added, per 10 μ L of hole, under the same terms
Continue to cultivate 2h, measures the absorbance value in each hole under 450nm wavelength with microplate reader, inhibiting rate is calculated as follows.Inhibiting rate=
(1- administration groups absorbance value/control group absorbance value) × 100%.
4, real-time fluorescence quantitative PCR detects Gli1mRNA, Gli2mRNA expression
Using 5.0 software Design primers of Primer, Gli1 upstream region of gene primers：5'-TCCAGCTAGAGTCCAGAGGT-
3', downstream primer：5'-TGGCTTGACTTGCACTTGTC-3'；Gli2 upstream region of gene primers：5'-
TGGCCGCTTCAGATGACAGATGTTG-3', downstream primer：5'-CGTTAGCCGAATGTCAGCCGTGAAG-3'；Internal reference
GAPDH sense primers：5'-AAGAAGGTGGTGAAGCAGGC-3', downstream primer：5'-ACCACCCTGTTGCTGTAGCC-3'.
Primer is synthesized by Shanghai Sheng Gong bio-engineering corporations.
Single cell suspension is made in HepG2 cells in exponential phase, is counted, kind is in 6 orifice plates, about per hole cell number
It is 1 × 106It is a；After cell is adherent, after culture to 80% fusion, serum free medium synchronization is changed；Add in 6 orifice plates later
The triptonide for entering various concentration is put into incubator and cultivates (control group not dosing) for 24 hours；Culture medium is discarded, is washed with PBS
It washs 2 times.TRIzol methods extract each group cell total rna respectively, and reverse transcription is cDNA.Reaction condition, which is arranged, is：95 DEG C of pre-degenerations
30s；95 DEG C of denaturation 5s, 60 DEG C of annealing 30s, totally 40 recycle.The target gene and reference gene of each sample are expanded simultaneously.Often
Group 3 repeating holes of cell design.Using 2-△△CtAnalytic approach is corrected by GAPDH gene levels.Ct values are in each reaction tube
Fluorescence signal cycle for being undergone when reaching the thresholding of setting, it is average by formula △ CT=CT average values (target gene)-CT
Value (reference gene) calculates separately the △ CT of administration group and control group, then by formula △ △ CT=△ CT administration group-△ CT controls
Group calculates 2-△△Ct, 2-△△CtIt is the relative expression quantity of Gli1mRNA, Gli2mRNA in each administration group HepG2 cells.
5, Westernblot experiments detection Gli1 albumen, Gli2 protein expression levels
Single cell suspension is made in HepG2 cells in exponential phase, is counted, kind is in 6 orifice plates, about per hole cell number
It is 1 × 106It is a；After cell is adherent, after culture to 80% fusion, serum free medium synchronization is changed；Add in 6 orifice plates later
The triptonide for entering various concentration is put into incubator and cultivates (control group not dosing) for 24 hours；Culture medium is discarded, is washed with PBS
It washs 2 times；Cell pyrolysis liquid is added, gently scrapes attached cell with cell scraper, is drawn in EP pipes, 4 DEG C, 15000rpm centrifugations
15min draws supernatant and obtains total protein of cell, and BCA methods carry out protein quantification；With total protein concentration SDS is carried out per 20 μ g loadings of hole
PAGE electrophoresis, transferring film；5% skimmed milk power is prepared with TPBS, pvdf membrane is closed, is positioned over 2h in 37 DEG C of shaking tables；By pvdf membrane plus
Enter by 1:In 1000 diluted GAPDH, Gli1, Gli2 antibody, 4 DEG C of shaking tables are incubated overnight；It is added by after proper proportion dilution
Secondary antibody, 37 DEG C of incubation 2h；ECL developer solutions are spread evenly across band corresponding position on film, in chemiluminescence imaging analyzer
Exposure；Interpretation of result is carried out using Image J image analysis softwares, the gray value of band is measured, calculates the purpose band of each group
With the ratio of internal reference, compare Gli1 albumen, Gli2 protein diversities between each group.
6, statistical analysis
Statistical disposition is carried out to the data obtained using 19.0 softwares of SPSS, data are indicated with mean value ± deviation, measurement data
Group difference compare using One-WayANOVA.
Three, experimental result
1, influence of the triptonide to HepG2 cell Proliferations
Compared with the control group, the HepG2 cell Proliferations of the basic, normal, high dosage administration group of triptonide are obviously suppressed,
Absorbance value significantly reduces (P ＜ 0.05).Table 1 and Fig. 1 are proliferation of the basic, normal, high dosage of triptonide to HepG2 cells
Inhibiting rate, it can be seen that apparent concentration dependent is presented in inhibiting effect.
Proliferation inhibition rate of the basic, normal, high dosage of 1 triptonide of table to HepG2 cells
2, influence of the triptonide to Gli1mRNA, Gli2mRNA expression in HepG2 cells
Compared with the control group, Gli1mRNA in the HepG2 cells of the basic, normal, high dosage administration group of triptonide,
Gli2mRNA expression is apparent to be suppressed, and target gene significantly reduces (P ＜ 0.05 or P ＜ with respect to the expression quantity of reference gene
0.01).Table 2 and Fig. 2 are Gli1mRNA, Gli2mRNA in the basic, normal, high dosage administration group HepG2 cells of triptonide
Relative expression quantity, it can be seen that apparent concentration dependent is presented in inhibiting effect.
The relative expression quantity of Gli1mRNA, Gli2mRNA in 2 each administration group HepG2 cells of table
3, influence of the triptonide to Gli1 albumen, Gli2 protein expression levels in HepG2 cells
Compared with the control group, Gli1 albumen, Gli2 in the HepG2 cells of the basic, normal, high dosage administration group of triptonide
Protein expression is obviously suppressed.Table 3 and Fig. 3 are Gli1 eggs in the basic, normal, high dosage administration group HepG2 cells of triptonide
In vain, the relative expression levels of Gli2 albumen, it can be seen that apparent concentration dependent is presented in inhibiting effect.
The relative expression quantity of Gli1 albumen, Gli2 albumen in 3 each administration group HepG2 cells of table
Above-described embodiment the experimental results showed that, triptonide can be by inhibiting Gli1, Gli2 gene expression aobvious
The proliferation for inhibiting HepG2 cells is write, and apparent dose dependent, triptonide Gli1, Gli2 is presented in inhibiting effect
Effective inhibitor of gene can be used for preparing the drug of prevention liver cancer.
Embodiment 2：Influence of the triptonide to human liver cancer SMMC-7721 systems cell Proliferation
One, experiment material
SMMC-7721 cell line is purchased from Shanghai Ji Kai gene technology Co., Ltd；
DMEM culture mediums, fetal calf serum and PBS are purchased from Gibco companies；TRIzol is purchased from Invitrogen companies；Reverse transcription
Kit is purchased from Fermentas companies of the U.S., and PCR kit for fluorescence quantitative is purchased from TaKaRa treasured bioengineering (Dalian) limited public affairs
Department；Cell pyrolysis liquid, SDS-PAGE albumen sample-loading buffer (5 ×), BCA albumen concentration determinations kit, 20 × TPBS bufferings
Liquid etc. is purchased from the green skies biotechnology research institute in Jiangsu, and pvdf membrane is purchased from Millipore companies of the U.S.；CCK-8 kits are purchased from
Japanese colleague's chemistry institute；Gli1, Gli2 and GAPDH primer are synthesized by Shanghai Sheng Gong bio-engineering corporations；
Rabbit-anti people Gli1 monoclonal antibodies, rabbit-anti people's Gli2 monoclonal antibodies are purchased from U.S. Santa Cruz
Biotechnology, the anti-human GAPDH monoclonal antibodies of mouse are purchased from Beijing Bioisystech Co., Ltd of Zhong Shan Golden Bridge.
Two, experimental method
1, human hepatocarcinoma BEL-7402 culture
Human hepatoma cell strain SMMC-7721 is in 37 DEG C, 5%CO2Under the conditions of, it is placed in green containing 10% fetal calf serum, 100U/mL
Secondary culture in the DMEM culture mediums of mycin and 100U/mL streptomysins passes on 1 time, logarithmic growth phase cell per 2d.
2, experiment packet
Triptonide low dosage administration group (7.5 μM)；
Triptonide middle dosage administration group (15 μM)；
Triptonide high dose administration group (30 μM)；
Control group：SMMC-7721 cells without any drug-treated.
3, CCK-8 methods measure cell proliferation inhibition rate
It is with reference to kit specification, the SMMC-7721 of exponential phase is cells trypsinised, centrifugation, with containing
The DMEM culture mediums of 10% fetal calf serum are made into cell suspension, and being seeded to 96 orifice plates makes cell density be 5 × 104/ mL is being saturated
Humidity, 37 DEG C, 5%CO2Under conditions of cultivate and make cell adherent for 24 hours.By whole mass concentration dosing, control group needed for above-mentioned grouping
Only plus 3 multiple holes are arranged in the PBS of pH7.4, each mass concentration, and CCK-8 48h after processing are added, per 10 μ L of hole, the same terms
Under continue cultivate 2h, the absorbance value in each hole is measured under 450nm wavelength with microplate reader, inhibiting rate is calculated as follows.Inhibiting rate
=(1- administration groups absorbance value/control group absorbance value) × 100%.
4, real-time fluorescence quantitative PCR detects Gli1mRNA, Gli2mRNA expression
Using 5.0 software Design primers of Primer, Gli1 upstream region of gene primers：5'-TCCAGCTAGAGTCCAGAGGT-
3', downstream primer：5'-TGGCTTGACTTGCACTTGTC-3'；Gli2 upstream region of gene primers：5'-
TGGCCGCTTCAGATGACAGATGTTG-3', downstream primer：5'-CGTTAGCCGAATGTCAGCCGTGAAG-3'；Internal reference
GAPDH sense primers：5'-AAGAAGGTGGTGAAGCAGGC-3', downstream primer：5'-ACCACCCTGTTGCTGTAGCC-3'.
Primer is synthesized by Shanghai Sheng Gong bio-engineering corporations.
Single cell suspension is made in SMMC-7721 cells in exponential phase, is counted, kind is in 6 orifice plates, per hole cell
Number about 1 × 106It is a；After cell is adherent, after culture to 80% fusion, serum free medium synchronization is changed；Later in 6 orifice plates
The middle triptonide that various concentration is added, is put into incubator and cultivates (control group not dosing) for 24 hours；Culture medium is discarded, is used
PBS is washed 2 times.TRIzol methods extract each group cell total rna respectively, and reverse transcription is cDNA.Reaction condition, which is arranged, is：95 DEG C pre-
It is denaturalized 30s；95 DEG C of denaturation 5s, 60 DEG C of annealing 30s, totally 40 recycle.The target gene and internal reference base of each sample are expanded simultaneously
Cause.3 repeating holes of every group of cell design.Using 2-△CtAnalytic approach is corrected by GAPDH gene levels.Ct values are each reaction
It is flat by formula △ CT=CT average values (target gene)-CT that fluorescence signal in pipe reaches the cycle undergone when the thresholding of setting
Mean value (reference gene) calculates separately the △ CT of administration group and control group, and as each group Gli1mRNA, Gli2mRNA is with respect to internal reference
The relative expression quantity of gene.
5, Western blot experiments detection Gli1 albumen, Gli2 protein expression levels
Single cell suspension is made in SMMC-7721 cells in exponential phase, is counted, kind is in 6 orifice plates, per hole cell
Number about 1 × 106It is a；After cell is adherent, after culture to 80% fusion, serum free medium synchronization is changed；Later in 6 orifice plates
The middle triptonide that various concentration is added, is put into incubator and cultivates (control group not dosing) for 24 hours；Culture medium is discarded, is used
PBS is washed 2 times；Be added cell pyrolysis liquid, gently scrape attached cell with cell scraper, be drawn in EP pipes, 4 DEG C, 15000rpm from
Heart 15min draws supernatant and obtains total protein of cell, and BCA methods carry out protein quantification；It is carried out per 20 μ g loadings of hole with total protein concentration
SDS PAGE electrophoresis, transferring film；5% skimmed milk power is prepared with TPBS, pvdf membrane is closed, is positioned over 2h in 37 DEG C of shaking tables；By PVDF
Film, which is added, presses 1:In 1000 diluted GAPDH, Gli1, Gli2 antibody, 4 DEG C of shaking tables are incubated overnight；It is added and is diluted by proper proportion
Secondary antibody afterwards, 37 DEG C of incubation 2h；ECL developer solutions are spread evenly across band corresponding position on film, are analyzed in chemiluminescence imaging
It is exposed in instrument；Interpretation of result is carried out using Image J image analysis softwares, the gray value of band is measured, calculates the purpose of each group
The ratio of band and internal reference compares Gli1 albumen, Gli2 protein diversities between each group.
6, statistical analysis
Statistical disposition is carried out to the data obtained using 19.0 softwares of SPSS, data are indicated with mean value ± deviation, measurement data
Group difference compare using One-WayANOVA.
Three, experimental result
1, influence of the triptonide to SMMC-7721 cell Proliferations
Compared with the control group, the apparent quilt of the SMMC-7721 cell Proliferations of the basic, normal, high dosage administration group of triptonide
Inhibit, absorbance value significantly reduces (P ＜ 0.05).Table 4 and Fig. 1 are the basic, normal, high dosage of triptonide to SMMC-7721
The proliferation inhibition rate of cell, it can be seen that apparent concentration dependent is presented in inhibiting effect.
Proliferation inhibition rate of the basic, normal, high dosage of 4 triptonide of table to SMMC-7721 cells
2, triptonide influences Gli1mRNA, Gli2mRNA expression in SMMC-7721 cells
Compared with the control group, Gli1mRNA in the SMMC-7721 cells of the basic, normal, high dosage administration group of triptonide,
Gli2mRNA expression is apparent to be suppressed, and target gene significantly reduces (P ＜ 0.05 or P ＜ with respect to the expression quantity of reference gene
0.01).Table 5 and Fig. 2 be Gli1mRNA in the basic, normal, high dosage administration group SMMC-7721 cells of triptonide,
The relative expression quantity of Gli2mRNA, it can be seen that apparent concentration dependent is presented in inhibiting effect.
The relative expression quantity of Gli1mRNA, Gli2mRNA in 5 each administration group SMMC-7721 cells of table
3, influence of the triptonide to Gli1 albumen, Gli2 protein expression levels in SMMC-7721 cells
Compared with the control group, Gli1 albumen in the SMMC-7721 cells of the basic, normal, high dosage administration group of triptonide,
Gli2 protein expressions are obviously suppressed.Table 6 and Fig. 3 are the basic, normal, high dosage administration group SMMC-7721 cells of triptonide
The relative expression levels of middle Gli1 albumen, Gli2 albumen.
The relative expression quantity of Gli1 albumen, Gli2 albumen in 6 each administration group SMMC-7721 cells of table
Above-described embodiment the experimental results showed that, triptonide can be by inhibiting Gli1, Gli2 gene expression aobvious
The proliferation of work inhibition SMMC-7721 cells, and the apparent dose dependent of inhibiting effect presentation, triptonide Gli1,
Effective inhibitor of Gli2 genes can be used for preparing the drug of prevention liver cancer.
Embodiment 3：Influence of the triptonide to hepatocellular carcinoma in nude mice growth of transplanted human
Growth conditions good exponential phase HepG2 cells are used into physiology after pancreatin digestion, centrifugation and trypan blue count
Brine is made 1 × 107The cell suspension of a/mL is inoculated in respectively at the right oxter 0.5cm of nude mice, and every nude inoculation 0.1mL is thin
Born of the same parents' suspension.Transplanted tumor in nude mice vernier caliper measurement transplantable tumor diameter, waits for tumour growth to about 100mm3When nude mice is divided at random
For triptonide low dose group (12.5mg/kg/d), triptonide high dose group (25mg/kg/d) and control group,
Every group 10.Triptonide group dosage regimen is：Gastric infusion, 1 time a day, control group give isometric solvent 0.5%
CMC-Na.Administration three weeks.After last time administration 6h, nude mice is put to death, tumor mass is stripped and weighs.According to administration group and control group tumor mass
Equal re-computation administration group tumor control rate (such as table 7).
7 triptonide group tumor control rate of table
| Triptonide low dose group | Triptonide high dose group | |
| In-vivo tumour inhibiting rate (%) | 35.5±4.9 | 69.8±5.3 |
Above-described embodiment the experimental results showed that, triptonide has the function of inhibiting liver cancer in vivo.
To sum up, triptonide can be by inhibiting Gli1, Gli2 gene expression to significantly inhibit liver cancer cells
Proliferation, and the apparent dose dependent of inhibiting effect presentation, effective inhibitor of triptonide Gli1, Gli2 gene,
It can be used for preparing the drug of prevention liver cancer.One skilled in the art will appreciate that inhibit Gli1, Gli2 gene expression be it is a kind of more
Ripe anti-cancer molecules access, triptonide are exactly based on this access and play antihepatocarcinoma effect.Simultaneously as tripterygium wilfordii
Lactone ketone is effective inhibitor of Gli1, Gli2 gene expression, and triptonide can be used for preparing treatment Gli1, Gli2
The drug of the relevant disease of gene high expression.
The effect of above-described embodiment is specifically to introduce the essentiality content of the present invention, but those skilled in the art should know
Protection scope of the present invention should not be confined to the specific embodiment by road.
Claims (6)
1. triptonide is used as the biomedical uses of Gli1 gene expression inhibitors.
2. triptonide is used as the biomedical uses of Gli2 gene expression inhibitors.
3. triptonide is used as preparing the biomedical uses of the drug of prevention liver cancer.
4. a kind of pharmaceutical preparation, it is characterised in that：Further include pharmaceutically including active constituent triptonide or its pharmaceutical salts
Pharmaceutically acceptable dosage form is made in acceptable carrier or excipient.
5. pharmaceutical preparation according to claim 4, it is characterised in that：The pharmaceutically acceptable carrier or excipient
Including one or more solids, semisolid or Auxiliary Liquid Material.
6. pharmaceutical preparation according to claim 4, it is characterised in that：The pharmaceutically acceptable dosage form includes piece
Agent, capsule, granule, injection, pill, syrup, powder, paste etc..
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| CN110496221A (en) * | 2019-01-03 | 2019-11-26 | 中山大学肿瘤防治中心（中山大学附属肿瘤医院、中山大学肿瘤研究所） | Inhibit application of the substance of DPPA3 expression in the product that preparation prevents and treats cancer |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110496221A (en) * | 2019-01-03 | 2019-11-26 | 中山大学肿瘤防治中心（中山大学附属肿瘤医院、中山大学肿瘤研究所） | Inhibit application of the substance of DPPA3 expression in the product that preparation prevents and treats cancer |
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