Application of decitabine and oxaliplatin in preparation of combination drug for treating renal cell carcinoma

A technology of oxaliplatin and decitabine, which is applied in the field of medicine and can solve problems such as unsatisfactory curative effect of solid tumors

Active Publication Date: 2014-11-19
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Decitabine (Dacogen, Eisai), a DNA methyltransferase inhibitor, was approved by the FDA in 2006 for the treatment of myelodysplastic syndrome, but its efficacy for solid tumors is not satisfactory

Method used

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  • Application of decitabine and oxaliplatin in preparation of combination drug for treating renal cell carcinoma
  • Application of decitabine and oxaliplatin in preparation of combination drug for treating renal cell carcinoma
  • Application of decitabine and oxaliplatin in preparation of combination drug for treating renal cell carcinoma

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] The invention provides the application of decitabine and oxaliplatin in the preparation of a combination drug for treating renal cell carcinoma, wherein the preferred molar concentration ratio of decitabine and oxaliplatin is 1:5-1:8.

Embodiment 2

[0022] Example 2 The combination of decitabine and oxaliplatin synergistically enhanced the sensitivity of renal cell carcinoma cell lines to both drugs.

[0023] 1. Reagents and materials:

[0024] Renal cancer cell lines 786-O [CRL-1932?, ATCC] and 769-P [CRL-1933?, ATCC] were purchased from Shanghai Cell Bank, Chinese Academy of Sciences. Both cell lines were cultured in RPMI-1640 medium (GIBCO, product number 31800022, added NaHCO 3 1.5 g / L, glucose 2.5 g / L, Sodium Pyruvate 0.11 g / L), and contains 10% high-quality fetal bovine serum. Culture conditions are 37°C, 5% CO 2 .

[0025] Decitabine was purchased from Sigma-Aldrich (5-Aza-2'-deoxycytidine, A3656). Oxaliplatin was purchased from China National Institutes for Food and Drug Control.

[0026] 2. Experimental method:

[0027] Decitabine, oxaliplatin stock solution and working solution preparation:

[0028] Using DMSO as a solvent, dilute decitabine and oxaliplatin to 1000 x stock solution and 250 x stock so...

Embodiment 3

[0048] The present invention finds that the combination of decitabine and oxaliplatin enhances the accumulation of oxaliplatin in the tumor cells of the renal cell carcinoma mouse model and enhances the sensitivity of the renal cell carcinoma mouse model to oxaliplatin.

[0049] 1. Reagents and Materials

[0050] Female Balb / C nude mice were purchased from Shanghai Experimental Animal Research Center. They were housed in the Experimental Animal Center of Zhejiang University.

[0051] Renal carcinoma cell line 786-O [CRL-1932?, ATCC] was purchased from Shanghai Cell Bank, Chinese Academy of Sciences. Both cell lines were cultured in RPMI-1640 medium (GIBCO, product number 31800022, added NaHCO 3 1.5 g / L, glucose 2.5 g / L, Sodium Pyruvate 0.11 g / L), and contains 10% high-quality fetal bovine serum. Culture conditions are 37°C, 5% CO 2 .

[0052] Decitabine was purchased from Sigma-Aldrich (5-Aza-2'-deoxycytidine, A3656). Oxaliplatin was purchased from China National Instit...

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Abstract

The invention provides an application of decitabine and oxaliplatin in preparation of a combination drug for treating renal cell carcinoma, wherein the molar concentration ratio of decitabine to oxaliplatin is 1:5-1:8, and the combination drug is prepared from decitabine, oxaliplatin and pharmaceutically acceptable auxiliary materials. In-vivo and in-vitro experimental researches prove that decitabine has an obvious synergistic effect on oxaliplatin in treatment of renal cell carcinoma, and the result expands the clinical application scope of decitabine and oxaliplatin. The combination drug provided by the invention can enhance accumulation of oxaliplatin in tumor cells of a renal cell carcinoma mouse model, and at the same time, enhances the sensitivity of the renal cell carcinoma mouse model to oxaliplatin.

Description

technical field [0001] The invention belongs to the field of medicine, and relates to the application of decitabine and oxaliplatin in the preparation of a combination drug for treating renal cell carcinoma. The combination of decitabine and oxaliplatin can significantly enhance the effect of oxaliplatin in treating renal cell carcinoma role. Background technique [0002] Renal cell carcinoma is the cancer with the highest mortality rate among urogenital tumors, and it is also the most common renal solid tumor. Its incidence accounts for about 90% of renal malignant tumors and 2-3% of the overall incidence of cancer. Except for early stage local renal cell carcinoma which can be cured by surgery, no breakthrough has been made in the treatment of metastatic renal cell carcinoma. Chemotherapy is one of the main ways to treat tumors at present, but the multidrug resistance of renal cell carcinoma often leads to the failure of chemotherapy. [0003] Combination drug therapy is...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/706A61P35/00A61K31/282
Inventor 曾苏刘彦卿郑小丽于琴琴王华谭付清蒋惠娣余露山
Owner ZHEJIANG UNIV
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