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Application of combined utilization of triptolide cisplatin in preparation of pancreatic cancer drug against drug resistance

A kind of triptolide and drug resistance technology, which is applied in the application field of preparing antitumor drug sensitizers

Inactive Publication Date: 2012-06-20
GUANGZHOU CELLPROTEK PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

According to our literature search, there has been no report on the synergistic enhancement of anti-cancer or anti-tumor effects of triptolide and cisplatin

Method used

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  • Application of combined utilization of triptolide cisplatin in preparation of pancreatic cancer drug against drug resistance
  • Application of combined utilization of triptolide cisplatin in preparation of pancreatic cancer drug against drug resistance
  • Application of combined utilization of triptolide cisplatin in preparation of pancreatic cancer drug against drug resistance

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Example 1 Triptolide enhances the induction of apoptosis by cisplatin on gemcitabine-resistant pancreatic cancer cell line PANC-1

[0033] 1) Determination of cell viability

[0034] Tumor cells were diluted with DMEM medium containing 10% (v / v) FBS and seeded into 96-well plates. Make the cell concentration 2 x 10 3 / well, 37℃, 5%CO 2 Incubate overnight. Drugs were then added and incubated for 48 hours. Then 20 ul of MTT solution was added to each well, and culture was continued for 4 h. Centrifuge at 1000 rpm for 10 min, carefully suck off the supernatant, add 100 ul of dimethyl sulfoxide to each well, and shake at low speed on a shaker for 10 min to fully dissolve the crystals. Measure the absorbance OD of each well at 570 nm (calibrated at 630 nm) in an enzyme-linked immunosorbent assay.

[0035] Cell viability = OD t / OD c ×100%

[0036] OD t , OD value of test group; OD c , OD value of the control group.

[0037] 2) Caspase-3 activity assay

[0038] ...

Embodiment 2

[0045] Example 2 Triptolide enhances the induction of apoptosis by cisplatin on gemcitabine-resistant pancreatic cancer cell MIA PaCa-2

[0046] Cell viability, caspase-3 activity, Hoechst 33342 staining and LDH release were the same as in Example 1.

[0047] In gemcitabine-resistant pancreatic cancer cells MIA PaCa-2, triptolide (TPL, 25 nM) or cisplatin (DDP, 16 μM) alone slightly reduced cell viability, whereas both drugs Combined application (TPL+DDP) significantly reduced the cell viability (compared with the control group, decreased by 59%). The combined therapy coefficient CI is lower than 1, revealing that the combined use of the two drugs is a synergistic effect. The cells were observed morphologically after Hoechst 33342 staining. Compared with other groups, the nuclei of the combined drug group were obviously condensed and fragmented. In the drug combination group, the activity of caspase-3, which plays an important role in cell apoptosis, was enhanced by 2.6 time...

Embodiment 3

[0049] Example 3 The synergistic induction of apoptosis by triptolide-cisplatin is mediated through the mitochondrial pathway

[0050] 1) Cytochrome C assay

[0051] Tumor cells ((2×10 6 / well) were inoculated into 6-well plates and cultured overnight to allow adhesion. Drugs were added and incubated for 48 hours. The cytoplasmic protein of each group was extracted, and then the cytoplasmic protein solution of each experimental group and the cytochrome C standard solution after serial dilution were added to a 96-well microtiter plate, 100 μl per well overnight. Add 3 wells for each sample to identify false positive results caused by differentiating positive results from contamination. The next day, the culture medium in the 96-well plate was aspirated, and the operation was performed according to the ELISA kit steps: wash once with wash solution, add assay diluent, 200 μl per well for 1 hour at room temperature. Add mouse anti-equine cytochrome C antibody diluted with ...

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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

[0001] technical field [0002] The invention relates to the application of triptolide and cisplatin in combination in the preparation of anti-drug-resistant pancreatic cancer drugs and in the preparation of anti-tumor drug sensitizers. Background technique [0003] Pancreatic cancer is a common gastrointestinal tumor with the characteristics of high malignancy, rapid invasion and high lethality. Due to the lack of effective means for early detection of pancreatic cancer and the rapid progression of the disease after diagnosis, most pancreatic cancer patients cannot be operated on. According to the latest estimate of the World Health Organization Cancer Research Center (GLOBOCAN 2008), there are 278,700 newly diagnosed pancreatic cancer cases and 26.27 deaths each year worldwide, with a mortality-incidence ratio of 0.94 [1]. Among all common malignant tumors, pancreatic cancer patients have the lowest survival rate, with an average median survival period of 3 months and a 5...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K33/24A61P35/00A61K31/585
Inventor 胡海燕朱文博李晶洁
Owner GUANGZHOU CELLPROTEK PHARMA
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