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Beclin1 基因过表达通过增强治疗诱导的宫颈癌 CaSki 细胞凋亡来提高化疗药物敏感性。

Over-expression of the Beclin1 gene upregulates chemosensitivity to anti-cancer drugs by enhancing therapy-induced apoptosis in cervix squamous carcinoma CaSki cells.

机构信息

Department of Obstetrics and Gynecology, Fujian Provincial Hospital, Fujian Provincial Clinical Medical College, Fujian Medical University, Fuzhou, Fujian 350001, PR China.

出版信息

Cancer Lett. 2010 Aug 28;294(2):204-10. doi: 10.1016/j.canlet.2010.02.001. Epub 2010 Mar 6.

Abstract

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.

摘要

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。

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