Department of Obstetrics and Gynecology, Fujian Provincial Hospital, Fujian Provincial Clinical Medical College, Fujian Medical University, Fuzhou, Fujian 350001, PR China.
Cancer Lett. 2010 Aug 28;294(2):204-10. doi: 10.1016/j.canlet.2010.02.001. Epub 2010 Mar 6.
The purpose of this study was to investigate whether the autophagy-related gene, Beclin1, plays a role in the regulation of chemosensitivity to anti-cancer drugs in cervical cancer CaSki cells. Expression of the Beclin1 protein was up-regulated in pcDNA3.1-Bec transfectants and led to cell arrest in the G(0)/G(1) phase of the cell cycle. The MTT assay indicated that over-expression of Beclin1 sensitized CaSki cells to chemotherapeutic drugs (cisplatin, paclitaxel, 5-fluorouracil, and epirubicin) and induced greater degrees of cytotoxicity than vector-only controls. After treatment with anti-cancer drugs, flow cytometric analysis indicated that the Beclin1-transfected group showed a greater increase in apoptosis than did the non-transfected group. Furthermore, pSUPER-Bec transfectants did not lead to a significant increase of resistance to each of these anti-cancer drugs. These results suggest that Beclin1 plays an important role in the regulation of potent anti-tumor activity, and over-expression of Beclin1 in CaSki cells may enhance apoptosis signaling induced by anti-cancer drugs.
本研究旨在探讨自噬相关基因 Beclin1 是否在调控宫颈癌 CaSki 细胞对抗癌药物的化疗敏感性中发挥作用。pcDNA3.1-Bec 转染子中 Beclin1 蛋白的表达上调导致细胞周期 G0/G1 期停滞。MTT 检测表明,Beclin1 的过表达使 CaSki 细胞对化疗药物(顺铂、紫杉醇、5-氟尿嘧啶和表柔比星)敏感,并诱导比空载体对照更高的细胞毒性。用抗癌药物处理后,流式细胞术分析表明,与未转染组相比,Beclin1 转染组的细胞凋亡增加更为明显。此外,pSUPER-Bec 转染子不会导致对这些抗癌药物的耐药性显著增加。这些结果表明,Beclin1 在调节有效的抗肿瘤活性中发挥重要作用,并且在 CaSki 细胞中过表达 Beclin1 可能增强抗癌药物诱导的细胞凋亡信号。