目的:研究新的耐药相关基因TCRP1在口腔鳞癌组织中的表达及其与顺铂临床疗效的关系,同时对TCRP1的作用机制进行初步探索。方法:采用免疫组织化学法检测TCRP1在舌癌组织中的表达及其与临床顺铂化学治疗疗效之间及体外药敏实验的相关性,Western印迹法及免疫共沉淀甄别TCRP1下游的作用分子。结果:在TCRP1低表达的患者中,缓解率达84.62%,而高表达患者组中缓解率为37.5%。体外药敏结果显示类似的结果。TCRP1表达改变影响Akt信号通路分子的表达,而且TCRP1与Akt存在物理上的相互结合。结论:TCRP1的表达影响口腔鳞癌的顺铂化学治疗疗效。TCRP1介导顺铂耐药的作用机制至少部分与TCRP1对Akt信号通路调节有关。
Objective: To investigate the correlation between expression of TCRP 1 gene and dinical cisplatin chemotherapy response in oral squamous cell carcinoma and to explore the functional mechanism of TCRP1 gene. Methods: Immunohistochemical methods were used to detect the expression of TCRP1 in oral squamous cell carcinoma tissues. The correlation between the expression of TCRP 1 and clinical chemotherapy response or the sensitivity of tongue cancer cells to cisplatin in vitro was analyzed. Western blot and co-immunoprecipitation were used to identify the down-stream functional target ofTCRP1. Results: In the group of low expressed TCRP1, the clinical cisplatin-based chemotherapy response rate was 84.62%, whereas, in the group of over-expressed TCRP 1, the rate was 37.5%. The drug sensitivity assay in vitro indicated similar tendency. TCRP 1 expression altered the expression pattern of Akt signal pathway molecules, and there was an interaction in physics between TCRP1 and Akt.Conclusion: TCRP1 plays a critical role in contributing to response of oral squamous cell carcinoma to cisplatin- based chemotherapy, which is involved, at least partly, in modulation of Akt pathway.