Basic Research for elucidation of chemo-resistance in mucinous adenocarcinoma cell.

(1)在PI3K抑制剂存在的情况下，CDDP诱导的细胞生长抑制在所有细胞系中均可忽略不计。我们观察到CDDP与MEK抑制剂联合使用时，CDDP的细胞毒性降低。有趣的是，当CDDP与PMA联合使用时，所有对CDDP有抗性的细胞的细胞生长都被显著抑制。经CDDP和PMA处理后，CDDP耐药细胞中处于G0/G1期和G2/M期的细胞比例下降，处于s期的细胞比例急剧增加，细胞周期分布转移到亚G1期。(2) CDDP和PMA可延长携带卵巢癌细胞的裸鼠的存活时间。

(1) A negligible increase in inhibition of cell growth induced by CDDP was detected in the presence of PI3K inhibitor in all cell lines. We observed a decrease the cytotoxicity of CDDP when CDDP was combined with MEK inhibitor. Interestingly, cell growth was dramatically suppressed when CDDP was combined with PMA in all the cells that were resistant to CDDP. After treatment with CDDP and PMA, the proportion of the cells in G0/G1 phase and G2/M phase were decreased, and the proportion of cells in the S-phase fraction was dramatically increased, and then the cell cycle distribution was shifted to the subG1 phase in the CDDP resistant cells.(2) Treatment with CDDP and PMA prolonged survival in nude mice bearing ovarian cancer cells.