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目的:研究肽酰脯氨基顺反异构酶B(peptidyl-prolyl cis-trans isomerase,PPIB)蛋白对结肠癌细胞成瘤的影响,探讨结肠癌低氧发病的机制。方法:应用RNAi技术,构建下调PPIB蛋白表达的稳转结肠癌细胞株,移植到BALB/c裸鼠皮下,检测PPIB蛋白下调组与对照组的成瘤差异。TUNEL法检测两组移植瘤的细胞凋亡水平。低氧培养结肠癌细胞株,Western印迹法检测PPIB的表达水平与低氧诱导因子1α(hypoxia-inducible factor-1α,HIF-1α)的关系。结果:下调PPIB蛋白表达后,在裸鼠皮下成瘤的能力显著减弱。SW480-si PPIB下调组的移植瘤体积显著小于SW480-NC对照组(P<0.01)。TUNEL检测显示下调组的癌细胞凋亡比例显著高于对照组(P<0.001)。在低氧环境下培养后,结肠癌细胞的PPIB蛋白表达水平随着低氧条件下HIF-1α的上调而升高(P<0.05)。结论:PPIB蛋白在结肠癌中因为低氧环境而表达升高,且在升高后通过抑制癌细胞的凋亡而发挥促进结肠癌形成和进展的作用,是一个极具临床应用价值的防治结肠癌的分子靶点。
Objective: To study the effect of peptidyl-prolyl cis-trans isomerase (PPIB) on the tumorigenesis of colon cancer cells and to explore the mechanism of hypoxia in colon cancer. Methods: RNAi technique was used to construct stable metastatic colon cancer cell line which down - regulated the expression of PPIB protein and transplanted into BALB / c nude mice subcutaneously. The difference of tumorigenicity between PPIB protein and control group was detected. TUNEL method was used to detect the apoptosis of the two groups. The colon cancer cell lines were cultured in hypoxia. The expression of PPIB was examined by Western blotting. The expression of hypoxia inducible factor-1α (HIF-1α) was detected by Western blot. Results: After the expression of PPIB protein was down-regulated, the ability of subcutaneous tumor formation in nude mice was significantly weakened. The tumor volume of SW480-si PPIB down-regulated group was significantly smaller than that of SW480-NC control group (P <0.01). TUNEL assay showed that the proportion of cancer cells in the down-regulated group was significantly higher than that in the control group (P <0.001). After cultured in hypoxia, the expression of PPIB protein in colon cancer cells increased with the increase of hypoxia HIF-1α (P <0.05). CONCLUSION: The expression of PPIB protein is increased in hypoxia environment in colon cancer and plays an important role in the prevention and treatment of colon cancer by inhibiting the apoptosis of cancer cells after it is elevated Molecular target of cancer.