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Abstract：
Objective: This research aimed to explore the function of protease activated receptor 2 (PAR-2) in oral squamous cell carcinoma (OSCC) development and progression, as well as underlying molecular mechanism.Methods: Tissue samples were collected from 115 OSCC patients. Quantitative real-time PCR (qRT-PCR) was performed to measure the expression of PAR-2 mRNA in OSCC tissues and cells. MTT and Transwell assays were used to detect the proliferation, migration, and invasion of OSCC cells, respectively. Western blot was performed to determine protein expression.Results: The expression of PAR-2 mRNA was up-regulated in OSCC tissue and cells (P<0.01), and its mRNA level was obviously correlated to tumor differentiation and TNM stage in OSCC (P<0.05 for both). The activation of PAR-2 with PAR-2AP (PAR-2 agonist) significantly promoted the proliferation, migration, and invasion of OSCC cells, while its knockout could inhibit malignant behaviors of OSCC cells (P<0.05). Excessive activation of PAR-2 enhanced phosphorylation level of PI3K, AKT, and mTOR revealing the activation of PI3K/AKT pathway. Moreover, LY294002, the inhibitor of PI3K/AKT pathway, could reverse oncogenic action caused by PAR-2 activation.Conclusion:PAR-2 can promote OSCC growth and progression via activating PI3K/AKT signaling pathway.
摘要：
目的:探讨蛋白酶激活受体2(PAR-2)在口腔鳞状细胞癌(OSCC)发生发展中的作用,以及潜在的分子机制。方法：收集115例OSCC患者的组织样本。进行定量实时PCR(qRT-PCR)以测量OSCC组织和细胞中PAR-2mRNA的表达。MTT法和Transwell法检测细胞增殖,迁移,和OSCC细胞的侵袭，分别。进行蛋白质印迹以确定蛋白质表达。结果:OSCC组织和细胞中PAR-2mRNA表达上调(P<0.01)。其mRNA水平与OSCC的分化程度和TNM分期明显相关(P<0.05)。PAR-2的激活与PAR-2AP（PAR-2激动剂）显著促进增殖，迁移,和OSCC细胞的侵袭，而其敲除可以抑制OSCC细胞的恶性行为(P<0.05)。PAR-2的过度激活增强了PI3K的磷酸化水平,AKT,和mTOR揭示PI3K/AKT通路的激活。此外，PI3K/AKT通路抑制剂LY294002,可以逆转PAR-2激活引起的致癌作用。结论:PAR-2可通过激活PI3K/AKT信号通路促进OSCC的生长和进展。
