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Application of SGLT2 inhibitor to preparation of product for improving sensitivity of antitumor drug

A technology of anti-tumor drugs and inhibitors, applied in the field of biomedicine, can solve problems such as large side effects and drug resistance

Active Publication Date: 2021-03-05
SHENZHEN GRADUATE SCHOOL TSINGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, chemotherapy often has the disadvantages of large side effects and tumor cells are prone to drug resistance.

Method used

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  • Application of SGLT2 inhibitor to preparation of product for improving sensitivity of antitumor drug
  • Application of SGLT2 inhibitor to preparation of product for improving sensitivity of antitumor drug
  • Application of SGLT2 inhibitor to preparation of product for improving sensitivity of antitumor drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0062] Example 1, Synergistic effect detection of CAN and antineoplastic drug doxorubicin

[0063] 1. Experimental materials

[0064] 1. Compounds: Canagliflozin (CAN for short) and Doxorubicin (Doxo for short) are both products of MedChemExpress (MCE). The article number of canagliflozin is HY-10451, and the article number of doxorubicin is HY-15142A.

[0065] 2. Cell source: Human liver cancer cells (HepG2), human colon cancer cells (HCT116), and human breast cancer cells (MCF7) are all products of Shanghai Cell Bank Company, Chinese Academy of Sciences. Adriamycin-resistant human liver cancer cells (HepG2-ADR) are Products of Shanghai Ayan Biotechnology Co., Ltd.

[0066] 3. Cell biology reagents: DMEM high-sugar powder medium (CP2205) and trypsin (Trypsin, R001100) are products of ThermoFisher Scientific; fetal bovine serum (FBS, P30-3302) is a product of Pan Biotech. Thiazolium blue reagent (MTT, 97062-378) is a product of Amreso Company.

[0067] 4. Experimental cons...

Embodiment 2

[0101] Example 2, the impact of CAN on the expression level of P-glycoprotein and its mechanism research

[0102] 1. Experimental materials

[0103] 1. Biochemical reagents: P-gp (ab170904) is a product of Abcam; P62 (#88588) is a product of Cell Signal Technology; LC3 (L7543) is a product of Sigma; β-actin antibody (A1978) is a product of Sigma Products; proteasome inhibitor MG132 (HY-13259) is a product of MedChemExpress; autophagy inhibitor BafA1 (HY-100558) is a product of MedChemExpress.

[0104] 2. Molecular biology reagents: siRNA is a product of Guangzhou Ruibo Biotechnology Co., Ltd.; Trizol is a product of Invitrogen (15596-026); Oligo dT, RNase inhibitor (RRI), dNTP (10mM) M-MLV reversal Recording enzyme, M-MLV 5×buffer, and SYBR Green are all products of Takara Company; primers were synthesized by Invitrogen Company, and the primer sequences are shown in Table 1.

[0105] Table 1. Primer sequences

[0106] Primer Forward sequence (Forward) Reverse ...

Embodiment 3

[0148] Example 3, Research on the Effect of CAN and Doxorubicin on HepG2 Autophagy

[0149] 1. Experimental materials

[0150] 1. Biochemical reagents: P62 (#88588) is a product of Cell Signal Technology; LC3 (L7543) is a product of Sigma; ULK1 (#8054) is a product of Cell Signal Technology; p-ULK1 (#6888P) is a product of Cell Signal Technology The product of Signal Technology Company, mTOR (#2983) is the product of Cell Signal Technology Company, p-mTOR (#5536) is the product of Cell Signal Technology Company, β-actin antibody (A1978) is the product of Sigma Company; EBSS (14155 -063) is a product of Gibco; Rapamycin (HY-10219) is a product of MedChemExpress; autophagy inhibitor Bafilomycin A1 (HY-100558) is a product of MedChemExpress.

[0151] 2. Experimental apparatus: the same as the apparatus in Example 2.

[0152] 3. Other reagents: the same as those in Example 1.

[0153] 2. Experimental method

[0154] With the method in embodiment 2.

[0155] 3. Experimental re...

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PUM

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Abstract

The invention discloses an application of an SGLT2 inhibitor to preparation of a product for improving sensitivity of an antitumor drug. The inventor finds that the SGLT2 inhibitor Canagliflozin can inhibit the autophagy phenomenon of stress protection generated by tumor cells during chemotherapeutic drug treatment by inhibiting the expression and functions of P-glycoprotein in the tumor cells, sothat the sensitivity of the tumor cells to chemotherapeutic drugs is improved, and the treatment effect of the drug is enhanced. The inhibitor of the type can exist in the form of liquid, dry powderor extract, can be made into capsules, tablets, injections, pills, granules, powder and other various dosage forms with health-care or medicinal effects together with various conventional auxiliary materials, and can be combined with other chemotherapeutic drugs to be used for treating malignant tumors.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and specifically relates to the application of SGLT2 inhibitors in the preparation of products for improving the sensitivity of antitumor drugs, enhancing the therapeutic effect of antitumor drugs and treating tumors. Background technique [0002] Malignant tumors are caused by genetic and environmental carcinogens that cause cells in local tissues of the human body to lose their normal regulation at the gene level and develop into cancer cells, which have three characteristics: infinite proliferation, metastasis and transformation. Malignant tumors not only seriously endanger human health, but also have a great impact on the lives of patients, and also pose a large medical burden on families and society. The number of cases and deaths of malignant tumors in my country ranks first in the world, and it is the most serious public health problem at present, which is not conducive to social stabi...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K45/06A61P35/00A61K31/704A61K31/381
CPCA61K45/00A61K45/06A61P35/00A61K31/381A61K31/704A61K2300/00
Inventor 谢伟东钟今孙鹏博丁艺佩张雅鸥许乃寒
Owner SHENZHEN GRADUATE SCHOOL TSINGHUA UNIV
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