TCRP1 promotes radioresistance of oral squamous cell carcinoma cells via Akt signal pathway
TCRP1 promotes radioresistance of oral squamous cell carcinoma cells via Akt signal pathway
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TCRP1通过Akt信号通路促进口腔鳞癌细胞的放射抗性
DOI：
10.1007/s11010-011-0880-8
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发表时间：
2011-11-01
影响因子：
4.3
通讯作者：
He, Zhimin
中科院分区：
文献类型：
--
作者：
Gu, Yixue;Fan, Shasha;He, Zhimin
舌癌耐药相关蛋白1（TCRP 1）是位于人类染色体11q13.4上的一个新基因，已被报道为与顺铂化疗耐药性相关的候选基因。结果表明，TCRP也有助于口腔鳞状细胞癌（OSCC）细胞的放射抗性。我们建立了TCRP 1过表达的Tca 8113/TCRP 1细胞系、TCRP 1敲低的Tca 8113/PYM-siRNA细胞系和配对的对照细胞系，为研究TCRP 1介导的放射反应在口腔鳞癌中的作用和机制提供了细胞模型。在这项研究中，我们首先比较了上调/下调TCRP 1表达的细胞系和配对对照细胞系的放射敏感性，通过克隆形成存活测定，Hoechst 33258染色，细胞生长测定，彗星试验。结果表明，TCRP 1通过减少细胞凋亡、增加细胞增殖和长期存活，在介导口腔鳞癌辐射抗性中发挥重要作用。进一步研究发现TCRP 1通过上调Akt活性和水平，进而上调NF-κB B水平发挥作用。这些结果为TCRP 1与口腔鳞癌辐射敏感性的关系提供了有力的证据，并为TCRP 1作为口腔鳞癌辐射敏感性评价的潜在分子标志物提供了理论依据。
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.