胡燕等

[摘要] 目的 探讨索拉非尼联合蒽环类化疗药表阿霉素对乳腺癌MCF-7细胞增殖周期的作用。 方法 细胞做四甲基偶氮唑盐实验，绘制细胞增殖曲线。实验分为4组：对照组、索拉非尼单药组、表阿霉素单药组、联合组（索拉非尼+表阿霉素）。用聚酰亚胺染色后，经流式细胞仪检测各组细胞增殖周期的变化。 结果 细胞增殖曲线可见细胞传代后开始增殖，4～5 d达到峰值，后随着时间的延长，细胞增殖受抑越来越明显。流式细胞仪检测细胞周期结果显示，索拉非尼单药组使MCF-7细胞阻滞于G0/G1期[（62.837±0.511）%]与对照组[（49.250±0.826）%]比较，差异有统计学意义（P < 0.05）；表阿霉素单药组使细胞阻滞于S期[（24.976±0.409）%]，与对照组[（23.473±1.009）%]比较，差异有统计学意义（P < 0.05）；联合组G0/G1期细胞比率[（64.373±0.429）%]高于对照组及表阿霉素单药组[（50.980±0.403）%]，差异均有统计学意义（均P < 0.05）。 结论 索拉非尼和表阿霉素的联合应用可以使乳腺癌MCF-7细胞明显阻滞于G0/G1，可以为乳腺癌的联合化疗提供一定的理论依据。

[关键词] 乳腺癌；生物化疗；索拉非尼；表阿霉素

[中图分类号] R979.1 [文献标识码] A [文章编号] 1673-7210（2014）09（c）-0035-04

Affect of the Coadministration of Sorafenib and anthracycline chemotherapy drug on the cell cycle of breast cancer MCF-7 cell

HU Yan WU Bing ZHANG Jun WANG Lianghe GE Wei LUO Rongcheng

Oncology Center， Renmin Hospital of Wuhan University， Hubei Province， Wuhan 430060， China

[Abstract] Objective To investigate the affect of Sorafenib combined with anthracycline chemotherapy Epirubicin on the proliferation of breast cancer MCF-7 cell cycle. Methods Cells growth curve were drawn after the MTT experiment. Four different groups were set up： control group， Sorafenib group， EPI group and Sorafenib+EPI （combination） group. The change of cell cycles were detected by PI single staining and flow cytometry. Results Cell growth curve showed， passaged cells began to proliferate， and reached the peak after 4-5 days， with the prolongation of time， cell proliferation was inhibited more and more obvious. The cell cycle by flow cytometry showed that， the Sorafenib group [（62.837±0.511）%] induced G0/G1 phase mitosis arrest， compared with control group [（49.250±0.826）%]， the difference was statistically significant （P < 0.05）； the EPI group （24.976±0.409）%] induced accumulation of S phase mitosis arrest， compared with control group [（23.473±1.009）%]， the difference was statistically significant （P < 0.05）； and the combination group [（64.373±0.429）%] showed greater increase of G0/G1 phase， compared with control group and EPI group [（50.980±0.403）%]， the differences were statistically significant （P < 0.05）. Conclusion The combined application of Sorafenib and Epirubicin can make the breast cancer MCF-7 cells arrested in G0/G1， provide certain theoretical basis for the combination chemotherapy for breast cancer.

[Key words] Breast cancer； Biochemotherapy； Sorafenib； Epirubicin

乳腺癌是女性最常见恶性肿瘤之一，占世界所有新发癌症的23%，占癌症总病死率的14%[1]。近期的流行病学调查中发现，在乳腺癌的远期随访中，复发性乳腺癌的预后很不理想[2]。目前对于晚期乳腺癌，尤其是性激素受体阴性的乳腺癌，由于缺乏特异性的靶标，一直没有理想的治疗方法[3]。传统化疗药费用昂贵，副作用大，而且容易使乳腺癌产生化疗抵抗。细胞周期失控是肿瘤细胞异常增殖的一个重要原因，在肿瘤中发现有调控细胞周期进程的Cyclin及细胞周期蛋白依赖性激酶（cyclin-dependent kinase，CDK）基因的异常表达[4]。细胞周期的异常运转是肿瘤细胞恶性增殖的核心环节，其中S期的DNA合成和G2/M期的细胞有丝分裂对维持肿瘤细胞的恶性增殖尤为重要。各种抗肿瘤药物对肿瘤细胞的生长抑制大都体现在对于细胞周期这两个时相的调控上[5]。……