粉防己碱逆转耐阿霉素的人乳腺癌MCF-7细胞的抗凋亡作用

REVERSAL OF ANTI-APOPTOTIC ACTION BY TETRANDRINE IN THE HUMAN BREAST CARCINOMA DOXORUBICIN-RESISTANCT MCF-7 CELLS

肿瘤细胞的多药耐药性与抗细胞凋亡作用关系密切。本研究用抗肿瘤药物阿霉素 (5μmol· L- 1 )处理人乳腺癌敏感和耐药的 MCF- 7细胞 2 4hr后 ,观察到在敏感细胞中 ,有较多的漂浮细胞 ,阿霉素主要分布在细胞核中 ;而在耐药细胞中 ,细胞形态未发生变化 ,阿霉素主要分布在细胞质中 ,其含量明显减少。阿霉素诱导 MCF- 7细胞的凋亡作用进一步用 An-nexin V - FITC染色法证实。此外 ,用高效逆转耐药性的药物粉防己碱 (2 0μmol· L- 1 )与阿霉素合用处理敏感和耐药的细胞 ,用线粒体荧光染料 Mitosensor TM染色 ,证明合用组凋亡细胞明显增多。通过流式细胞术分析显示 :细胞凋亡的发生与细胞周期无关。本研究表明 :粉防己碱能逆转耐阿霉素的人乳腺癌 MCF- 7细胞的抗凋亡作用。

There is a close relationship between multidrug resistance and antiapoptotic action in tumor cells. Both sensitive and drug resistant MCF 7 human breast carcinnoma cells were treated by antitumor drug doxorubicin (5 μmol.1 -1 ) for 24 hours. A large number of floating cells could be observed in sensitive tumor cells, and the doxorubicin was largely distributed in nuclei, whereas doxorubicin was distributed in cytoplasm and no morphological changes could be observed in drug resistant tumor cells after treatment. The induction of apoptosis in sensitive and drug resistant MCF 7 cells was confirmed by Annexin V FITC method. By using mitosensor staining chondria dye, the combination of doxobubicin with tetraandrine, a highly effective agent for reversal of multidrug resistance, could significantly increase the number of apoptotic cells in sensitive tumor cells. The occurrence of apoptosis was unrelated with cell cycle in both sensitive and drug resistant MCF 7 cells using analysis of flow cytometry. The results demonstrated that tetrandrine could effectively reverse anti apoptotic action and enhance induction of apoptosis by doxorubicin in the drug resistant and sensitive human breast carcinoma MCF 7 cells.\;