格列卫增加获得性他莫昔芬耐受MCF—7细胞对阿霉素的敏感性

Glivec enhances the down-regulated cytotoxicity of adriamycin in acquired tamoxifen-resistant MCF-7 cell line.

OBJECTIVE: To study the alteration of bax, bcl-2, p170 expressing and the second effect on the adriamycin (ADR) induced cytotoxicity in acquired tamoxifen (TAM)-resistant MCF-7 cell line. METHODS: The bax, bcl-2, p170 protein expressions were detected by flow cytometry respectively, as well as the content of intracellular ADR. The in vitro adenosine triphosphate tumor chemosensitivity assay (ATP-TCA) was performed to evaluate the cytotoxicity of ADR, and also the effect of Glivec on the cytotoxicity of ADR. RESULTS: The percentages of bax, bcl-2 expressions in the acquired TAM resistant MCF-7 were down-regulated from 53.17+/-1.45% to 28.70+/-1.41% (P <0.01), 41.53+/-2.17% to 37.87+/-1.86% P >0.05 respectively, the p170 was up-regulated from 27.43+/-2.16% to 32.13+/-1.31% (P <0.05), after a 16-week-treatment with 1 x 10(-7) mol/L TAM. Accordingly, the chemosensitivity and the fluorescence intensity of intracellular ADR declined, both of them can be significantly reversed by 10 microg/ml Glivec. CONCLUSION: The acquired TAM resistant MCF-7 accompanied with a declined ADR cytotoxicity, down-regulation of bcl-2/bax-induced apoptosis and up-regulation of p170-induced drug efflux may had a synergic devotion. Glivec may enhance the cytotoxicity of ADR on the acquired TAM-resistant MCF-7 cell line.