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卡铂(carboplatin,CBP)是一种抗肿瘤活性较强的化疗药物,通过诱导细胞周期阻滞抑制肿瘤细胞生长,但其诱导细胞周期阻滞的报告不甚一致.本研究探索卡铂对卵巢癌HO-8910细胞生长及细胞周期进程的影响.MTS结果显示,卡铂以浓度和时间依赖方式抑制卵巢癌HO-8910细胞生长,联合使用ERK1/2通路抑制剂PD98059可使卡铂抗卵巢癌细胞增殖作用增强.采用Giemsa染色法观察到,卡铂与PD98059单用或联用均能致卵巢癌细胞发生明显的形态学变化.流式细胞术检测细胞周期发现,随卡铂浓度的增高,S期阻滞作用增强;抑制ERK1/2通路可拮抗卡铂对HO-8910细胞S期阻滞作用,增加G1期阻滞作用,而对G2/M期细胞影响不明显.Western印迹结果显示,随卡铂浓度的增高,p-ERK1/2、Cdc2(Y15)和p-Cdc2(T161)的表达逐渐升高,Cyclin E1和Cyclin B1的表达逐渐降低;抑制ERK1/2通路可将卡铂上调,p-ERK1/2和p-Cdc2(T161)的作用反转为下调作用,上调Cdc2(Y15)的表达受阻,抑制Cyclin B1的下调作用,促进Cyclin E1的下调作用.本研究结果提示,卡铂通过抑制ERK1/2激活,诱导人卵巢癌HO-8910细胞S和G1期阻滞,抑制卵巢癌细胞生长.
Carboplatin (CBP), a chemotherapeutic drug with strong anti-tumor activity, inhibits the growth of tumor cells by inducing cell cycle arrest, but the report of cell cycle arrest is not consistent.This study explored the effect of carboplatin on ovarian The results of MTS showed that carboplatin inhibits the growth of ovarian cancer cell line HO-8910 in a concentration-and-time-dependent manner. Combined use of PD98059, an inhibitor of ERK1 / 2 pathway, Giemsa staining showed that carboplatin and PD98059 alone or in combination can cause significant morphological changes in ovarian cancer cells detected by flow cytometry cell cycle found that with the increase of carboplatin concentration, S phase arrest enhanced inhibition of ERK1 / 2 pathway can be antagonized carboplatin S-phase arrest of HO-8910 cells, increased G1 arrest, while the G2 / M phase cells had no significant effect.Western blot results showed that, The expression of p-ERK1 / 2, Cdc2 (Y15) and p-Cdc2 (T161) gradually increased and the expression of Cyclin E1 and Cyclin B1 decreased gradually with the increase of carboplatin concentration. Inhibition of ERK1 / 2 pathway upregulated carboplatin , the effects of p-ERK1 / 2 and p-Cdc2 (T161) were reversed to down-regulation Up-regulated the expression of Cdc2 (Y15), inhibited the down-regulation of Cyclin B1 and down-regulated the expression of Cyclin E1.The results of this study suggest that carboplatin induces the expression of S and G1 in human ovarian cancer cell line HO-8910 by inhibiting ERK1 / 2 activation Period block, inhibit ovarian cancer cell growth.