Tetrandrine Combined With Cisplatin And A Novel Hsp90 Inhibitor On The Role Of Human Breast Cancer Cells In Vitro

Chemotherapy is a primary mean of clinical cancer treatment at pressent. However, due to drug resistance of tumor cells, chemotherapy was not able to reach the desirably clinical effect. So improved tumor sensitivity to chemotherapeutic drugs was a key problem to cancer treatment. Recently, the new method of targeted therapy is based on the expression of genes or receptor to selective drugs, so the efficacy will be better and toxicity will be lower. Targeted therapy application was at primary stage now. Although it has potential prospects, but can not replace surgery,chemotherapy,radiotherapy treatment and other traditional treatment for cancer at present.In order to improve the sensitivity of cancer cells to chemotherapeutic drugs, and explore anti-tumor mechanism of the novel Hsp90 inhibitor SNX-2112, human breast cancer cells:MDA-MB-231,MCF-7 and MCF-7/ADR were selected as models in this study. Atomic force microscopy,confocal microscopy,MTT method,Annexin-v/PI fluorescence staining,flow cytometry and Western Blot methods were used to detect changes in the surface structure of cancer cells and drug-related protein, and the following results were obtained:1,The surface structure of tumor cells were damaged when treated with tetrandrine in low concentration at 24h and 48h. The S phase of cell cycle percentage was increased from 30.5%±0.30% to 51.7%±0.30%. Combination therapy is a way to reduce the concentration of cisplatin IC50 reduced from 26.33μmol/L to 13.32μmol/L. It was able to improve the sensitivity of tumors to chemotherapeutic drugs treatment, inhibit tumor growth.2,A novel Hsp90 inhibitor SNX-2112 can effectively inhibit the growth of MCF-7/ADR cells and the activity of receptor protein. MCF-7/ADR cell was treated with 10μmol/L SNX-2112 for 48 hours. The inhibition rate was (63.6±8.2)%, and apoptotic rate was (53.4±7.3)%. SNX-2112 can induce degradation in Hsp90 and apoptosis in breast cancer cells. It changed the normal expression of DNA repair enzyme PARP of cancer cell. The drug resistant effect of SNX-2112 is not effected by the glycoprotein expression. Atomic force microscopy and other biotechnology tools were used to detect the changes in the surface structure and morphology,toxicity and drug-related protein of tumor cells. We can see the effect of drugs on cells in visualization. Combination treatment was able to improve the sensitivity of cancer cells, and reduce the occurrence of drug resistance. SNX-2112 is a good effect of targeted therapy drugs, and is able to induce apoptosis in cancer cells. This study provides a new experimental reference for anti-cancer drug research.