Abstract:【Objective】To observe the effect of hypoxia on invasion and metastasis of hepatocellular carcinoma (HCC) cells and to investigate the mechanism of drug resistance in HCC cells induced by hypoxia.【Methods】HCC hypoxia model was established by using HepG2 and SMMC-7721 cells. The morphological changes were observed by inverted microscope; invasion and metastasis of tumor cells in vitro were detected by Transwell migration and invasion assays; the cell activity was tested by MTT assay. Epithelial mesenchymal transition (EMT) related protein including E-cadherin, Vinmentin, N-cadherin and the expression of tumor drug resistance gene ABCG2 were detected by Western blotting. Apoptosis and cell cycle changes were detected by flow cytometry.【Results】HCC cells transformed from epithelial like phenotype to mesenchymal cell like phenotype after 48 h of hypoxia culture; the expression of E-cadherin decreased significantly and the expression of Vimentin and N-cadherin increased significantly under hypoxia (P<0.05); at the same time, the migration and invasion ability of HCC cells increased significantly under hypoxia (P<0.05); hypoxia can lead to a significant increase in the number of HepG2 and SMMC-7721 arrested in quiescent phase (G0/G1); under hypoxia, the resistance of HCC cells to cisplatin was significantly increased (P<0.05); the expression of ABCG2 protein was increased under hypoxic conditions (P<0.05).【Conclusion】Hypoxia induces HCC EMT transformation and causes invasion and metastasis. At the same time, hypoxia may also induce resistance to cisplatin.
焦敏,经里,阮之平,梁璇,姚煜,南克俊. 缺氧诱导肝癌细胞EMT转化及耐药的初步实验研究[J]. 医学临床研究, 2017, 34(10): 1880-1884.
JIAO Min, JING Li, RUAN Zhi-ping, et al. Preliminary Study on HCC EMT Transformation and Drug Resistance Induced by Hypoxia. JOURNAL OF CLINICAL RESEARCH, 2017, 34(10): 1880-1884.