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γ射线辐射对p53野生型和缺陷型HCT116结肠癌细胞系细胞周期、细胞凋亡及端粒酶活性的影响

Effects of gamma irradiation on cell cycle, apoptosis and telomerase activity in p53 wild-type and deficient HCT116 colon cancer cell lines.

作者信息

Halacli Sevil Oskay, Canpinar Hande, Cimen Eren, Sunguroglu Asuman

机构信息

Pediatric Immunology Unit, Institute of Children's Health, Hacettepe University, Sihhiye, Ankara 06100, Turkey.

出版信息

Oncol Lett. 2013 Sep;6(3):807-810. doi: 10.3892/ol.2013.1441. Epub 2013 Jul 3.

Abstract

Radiotherapy serves as adjunctive treatment to chemotherapy and surgical resection of colorectal cancer. However, the cellular response to irradiation varies depending on the expression of tumor suppressor p53, which plays a significant role in the regulation of cell cycle arrest, apoptosis and telomerase activity in various cancers. The present study aimed to investigate cell cycle arrest, apoptosis and telomerase activity with respect to p53 expression in p53 wild-type (+/+) and deficient (-/-) HCT116 colon cancer cell lines following 5 Gy γ-irradiation. Cell cycle arrest and apoptosis were evaluated using flow cytometry. The telomerase activity was measured using a TRAP (telomerase repeat amplification protocol) assay. Following treatment with irradiation, G/S cell cycle arrest occurred in the p53+/+ cells, whereas the p53-/- cells accumulated in the G phase. No differences were observed in the apoptotic ratios between the two cell lines following irradiation. Decreased telomerase activity was observed in the p53+/+ cells, whereas telomerase activity was increased in the p53-/- cells. The results showed that while telomerase activity and G cell cycle arrest were regulated depending on the p53 status, G arrest and the apoptotic response were promoted via a p53-independent pathway.

摘要

放射治疗是结直肠癌化疗和手术切除的辅助治疗手段。然而,细胞对辐射的反应因肿瘤抑制因子p53的表达而异,p53在多种癌症的细胞周期停滞、凋亡和端粒酶活性调节中起重要作用。本研究旨在探讨5 Gy γ射线照射后,p53野生型(+/+)和缺陷型(-/-)HCT116结肠癌细胞系中,细胞周期停滞、凋亡及端粒酶活性与p53表达的关系。采用流式细胞术评估细胞周期停滞和凋亡情况。使用端粒酶重复序列扩增法(TRAP)检测端粒酶活性。照射处理后,p53+/+细胞出现G/S期细胞周期停滞,而p53-/-细胞则在G期积累。照射后,两种细胞系的凋亡率未见差异。p53+/+细胞中端粒酶活性降低,而p53-/-细胞中端粒酶活性升高。结果表明,虽然端粒酶活性和G期细胞周期停滞受p53状态调控,但G期停滞和凋亡反应是通过p53非依赖途径促进的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d5e/3789084/dda42323c1c7/OL-06-03-0807-g00.jpg

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