Zong Zhi-ping, Matsui Shinobu, Katsuda Shogo, Han Jian-feng, Fujikawa-Yamamoto Kohzaburo
Medical Research Institute, Division of Basic Science, Kanazawa Medical University, Uchinada-machi, Ishikawa 920-0293, Japan.
Eur J Pharmacol. 2004 Apr 5;489(1-2):3-11. doi: 10.1016/j.ejphar.2004.02.027.
Taxol was found to induce polyploidization and apoptosis in cultured methylcholanthrene-induced sarcoma cells (Meth-A cells), but some of the cells in G1 phase were not affected. We refer to these cells as taxol-resistant cells. Phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) regulator, was used to test the taxol-resistant cells. Many of the taxol-resistant cells disappeared after treatment with taxol in the presence of PMA. To explore the mechanism of this effect, we employed flow cytometry to determine levels of p53, p21, bcl-2 and caspase proteins in the taxol-resistant cells, and found that the expression of the bcl-2 protein was markedly decreased and the expression of the caspase protein markedly increased after treatment with taxol in the presence of PMA. These findings suggest that PMA enhances the sensitivity of taxol-resistant cells to taxol, and taxol treatment in the presence of PMA induces the apoptosis of taxol-resistant cells by inhibiting the expression of the bcl-2 protein and increasing the expression of the caspase protein.
已发现紫杉醇可诱导培养的甲基胆蒽诱导肉瘤细胞（Meth-A细胞）发生多倍体化和凋亡，但处于G1期的部分细胞不受影响。我们将这些细胞称为紫杉醇耐药细胞。佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA），一种蛋白激酶C（PKC）调节剂，被用于检测紫杉醇耐药细胞。许多紫杉醇耐药细胞在紫杉醇与PMA共同处理后消失。为探究此效应的机制，我们采用流式细胞术测定紫杉醇耐药细胞中p53、p21、bcl-2和半胱天冬酶蛋白的水平，发现紫杉醇与PMA共同处理后，bcl-2蛋白的表达明显降低，半胱天冬酶蛋白的表达明显增加。这些发现表明，PMA可增强紫杉醇耐药细胞对紫杉醇的敏感性，且紫杉醇与PMA共同处理通过抑制bcl-2蛋白的表达并增加半胱天冬酶蛋白的表达来诱导紫杉醇耐药细胞凋亡。
