PI3K p85α在大肠癌侵袭转移过程中的表达及意义

PI3K p85α expression and its role in the progression of colorectal cancer invasion and metastasis

目的研究PI3K p85α在大肠癌侵袭和转移过程中的表达及意义。方法用免疫组织化学二步法检测试剂盒检测123例大肠病变组织标本中PI3K p85α的表达情况,用等级相关的秩和检验分析PI3K p85α在大肠病变组织中表达的意义及其与临床病理特征间的关系;培养已成功沉默PI3K p85α表达的大肠癌Lovo细胞(PI3K p85α/RNAi-Lovo)及Lovo对照组细胞,肿瘤细胞侵袭实验(transwell)和划痕愈合实验观察PI3K p85α对lovo细胞的侵袭和转移能力的影响,明胶酶谱检测基质金属蛋白酶-2(MMP-2)的表达。结果 PI3K p85α蛋白在大肠癌癌变过程中表达阳性率呈递增趋势,差异有统计学意义(P<0.05)。PI3K p85α/RNAi-Lovo细胞组侵袭和转移能力明显低于对照组;MMP-2表达量及活性显著降低。结论 PI3K p85α蛋白可能在大肠癌的侵袭和转移中起重要作用,沉默PI3K p85α基因可以显著抑制其侵袭、转移和基质金属蛋白酶的分泌及活性,因而PI3K p85α影响lovo细胞的侵袭和转移可能与调控基质金属蛋白酶分泌密切相关。

Objective To investigate the influence of PI3K p85α on the invasion and metastasis of colorectal cancer.Methods The expression of PI3K p85α was evaluated in 85 normal colorectal tissue,colorectal adenoma,primary colorectal carcinoma and metastatic colorectal carcinoma specimens using immunohistochemical staining,and the relationship between the expression of PI3K p85α protein and the clinicopathological factors was analyzed.The PI3Kp85α/RNAi transfected cells（PI3K p85α/RNAi-Lovo） were cultured in RPMI1640,supplemented with 10% fetal calf serum and 500 g/ml G418.The cells were subjected to transwell assay and wound closure assay to determine the invasion and migration of PI3K p85α-depleted cells and the control cells.Expression of MMP-2 was detected by gelatin-zymography assays.Results The expression of PI3K p85α protein was significantly correlated with the progression of colorectal cancer（P0.05）.The invasion and metastatic ability of PI3K p85α/RNAi-Lovo were significantly lower than the control cells.Gelatin-zymography analysis showed that the expression and activity of MMP-2 was significantly suppressed in PI3Kp85α-knockdown cells than in the control cells.Conclusion PI3K p85α may play an important role in modulating human colorectal carcinoma cells invasion and metastasis,and PI3K p85α gene silencing can inhibit human colorectal cancer cell invasion and the activity of MMP-2.PI3Kp85α may affect invasion and metastasis of human colorectal carcinoma cells via the regulation of the activity of MMP-2.