Medicine for treating kidney renal cell carcinoma and application of medicine

A renal cell carcinoma and drug technology, applied in the field of biopharmaceuticals, can solve problems such as limiting the clinical application of sunitinib, achieve obvious synergistic effects, reduce drug resistance, and inhibit activity

Inactive Publication Date: 2020-09-25
YIXING PEOPLES HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Clinical data show that nearly one-third of mRCC patients have inherent resistance to sunitinib, while the remaining patients develop resistance to sunitinib after 6-15 months, which greatly limits the ability of sunitinib clinical application

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Example 1 Renal cell carcinoma cell sample screening

[0036] The expression of STC-2 in human renal carcinoma cells Caki-1, 796-P, 786-O, ACHN and HK-2 was detected by RT-PCR and Western blot. refer to figure 2 The results showed that the expression of STC2 in human renal carcinoma cell line 796-P was significantly higher than that in human renal tubular epithelial cell HK-2 (p figure 2 -A, B shown).

[0037] Therefore, Caki-1, 786-O, 769-P, etc. are more suitable for observing the expression level of STC-2. Therefore, these three groups were selected as the basis for subsequent experiments.

Embodiment 2

[0038] Example 2 Sunitinib Dosage Screening

[0039] After using sunitinib to treat the above selected cells for 2 days, use the MTT method to detect the proliferation of the cells, refer to image 3 As shown, sunitinib can significantly inhibit the cell viability of renal cancer cells Caki-1, 786-O, and 796-P. From image 3 It can be seen that Caki-1 cells are most sensitive to 5uM sunitinib, and 786-O and 796-P cells are dose-dependent to the drug sensitivity (such as image 3 -A shown). After 5uM sunitinib was treated for 1 day, there was no significant difference between the treatment group and the control group; after continuous treatment for 2 days and 3 days, the cell activity of the treatment group was significantly lower than that of the control group (such as image 3 -B shown); Compared with Caki-1 cells, 786-O and 796-P cells are more sensitive to sunitinib (as shown in image 3 -B shown).

[0040] Based on the above conclusions, 5uM sunitinib was subsequently...

Embodiment 3

[0041] Example 3 Effect of CRISPR / Cas9 Gene Knockout on Sunitinib Resistance

[0042] Through the STC-2 gene knockout vector virus (based on the STC2 CRISPR guide RNA sequence designed by the Feng Zhang laboratory of the Broad Institute, use the plasmid pX601-AAV-CMV to synthesize or purchase, such as abm's STC2 CRISPR Knockout Vector / Virus / Cell Line), AAV virus was used to transfect Caki-1 cells treated with 5uM sunitinib for 2 days, and the cells were collected for MTS detection after 48 hours of infection. 2d Caki-1 cells without other treatment decreased by 20%, showing that the low expression of STC2 mRNA reduces the drug resistance of sunitinib and improves its effect of inducing renal cell carcinoma apoptosis.

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Abstract

The embodiment of the invention discloses an application of a reagent for reducing stanniocalcin-2 level of patients suffering from kidney renal cell carcinoma to preparation of a medicine for treating kidney renal cell carcinoma. The medicine comprises the reagent for reducing stanniocalcin-2 level of patients suffering from kidney renal cell carcinoma, and a multi-target point tyrosine kinase inhibitor. The method provided by the invention can improve the treatment effects of the patients suffering from kidney renal cell carcinoma by restraining expression of stanniocalcin-2 and reducing thereverse tolerance of the multi-target point tyrosine kinase inhibitor.

Description

technical field [0001] The invention relates to the field of biopharmaceuticals, in particular to a medicine for treating renal cell carcinoma and its application. Background technique [0002] Renal Cell Carcinoma (RCC), referred to as kidney cancer, is a common malignant tumor of the urinary system, and its incidence rate ranks second among malignant tumors of the urinary system. The onset of RCC is insidious, nearly one-third of patients have metastasized at the time of first diagnosis, and 20-40% of RCC patients still develop metastasis after tumor resection, while patients with metastatic Renal Cell Carcinoma (mRCC) The prognosis of the disease is extremely poor, and the five-year survival rate does not exceed 10%, causing a great burden of treatment and physical burden. Although the incidence of kidney disease in my country is still at a low level compared with some countries and regions in the world, the incidence rate has shown an increasing trend year by year in re...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K39/395A61K31/404A61P35/00A61P13/12
CPCA61K31/404A61K39/39558A61K45/06A61P13/12A61P35/00A61K2300/00
Inventor 谢益敏秦振乾袁雪锋顾杰施海峰吴小红马铁梁
Owner YIXING PEOPLES HOSPITAL
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