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TCRP1 通过 Akt 信号通路促进口腔鳞状细胞癌细胞的放射抵抗性。

TCRP1 promotes radioresistance of oral squamous cell carcinoma cells via Akt signal pathway.

机构信息

Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha 410078, Hunan, China.

出版信息

Mol Cell Biochem. 2011 Nov;357(1-2):107-13. doi: 10.1007/s11010-011-0880-8. Epub 2011 May 21.

DOI:10.1007/s11010-011-0880-8
PMID:21603883
Abstract

Tongue cancer resistance-associated protein 1 (TCRP1) is a novel gene located on human chromosome 11q13.4 which has been reported as a candidate related to chemotherapeutic resistance to cisplatin. Results suggest that TCRP also contribute to radioresistance in oral squamous cell carcinoma (OSCC) cells. We previously established exogenous overexpression of TCRP1 cell line Tca8113/TCRP1 and TCRP1 knockdown cell line Tca8113/PYM-siRNA and paired control cell lines, which provides a cell model system to investigate the roles and mechanisms of TCRP1-mediated radioresponse in OSCC. In this study, we first compared the radiosensitivity of up/down-regulating expression of TCRP1 cell lines and paired control cell lines by a clonogenic survival assay, Hoechst 33258 staining, cell growth assay, and comet assay. The results indicated that TCRP1 played a significant role in mediating OSCC radioresistance through decreased cells apoptosis and increased cellular proliferation and long-term survival. The further study found that TCRP1 function by up-regulating Akt activity and levels and then elevating the level of NF-κB. In summary, these results provided strong evidence for the linkage between TCRP1 and radiation sensitivity and may provide theoretical base of TCRP1 as a potential molecular mark of estimating the response for irradiation in OSCC.

摘要

舌鳞癌耐药相关蛋白 1(Tongue cancer resistance-associated protein 1,TCRP1)是一个位于人类染色体 11q13.4 上的新基因,已被报道为与顺铂化疗耐药相关的候选基因。研究结果表明,TCRP1 也与口腔鳞状细胞癌(Oral squamous cell carcinoma,OSCC)细胞的放射抵抗有关。我们之前建立了外源性过表达 TCRP1 的 Tca8113/TCRP1 细胞系和 TCRP1 敲低的 Tca8113/PYM-siRNA 细胞系及其配对的对照细胞系,为研究 TCRP1 介导的 OSCC 放射反应中的作用和机制提供了细胞模型系统。在这项研究中,我们首先通过集落形成生存实验、Hoechst 33258 染色、细胞生长实验和彗星实验比较了上调/下调 TCRP1 细胞系及其配对对照细胞系的放射敏感性。结果表明,TCRP1 通过减少细胞凋亡、增加细胞增殖和长期存活,在介导 OSCC 放射抵抗中发挥重要作用。进一步的研究发现,TCRP1 通过上调 Akt 活性和水平,从而提高 NF-κB 的水平,发挥作用。总之,这些结果为 TCRP1 与辐射敏感性之间的联系提供了有力证据,并可能为 TCRP1 作为评估 OSCC 照射反应的潜在分子标志物提供理论基础。

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