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[目的]观察缺氧对肝癌细胞侵袭转移能力的影响,并进一步探讨缺氧环境下肝癌细胞耐药机制.[方法]利用HepG2、SMMC-7721细胞建立肝癌细胞缺氧模型,利用倒置显微镜观察细胞形态学变化;Transwell迁移与侵袭实验检测肿瘤细胞体外侵袭转移能力;MTT法检测肿瘤细胞活性;Western blot检测EMT相关蛋白E-cadherin、Vinmentin、N-cadherin和肿瘤耐药基因ABCG2的表达;采用流式细胞术检测凋亡和细胞周期变化.[结果]缺氧培养48h后的肝癌细胞从上皮细胞样表型转化为间质细胞样表型;缺氧条件下肝癌细胞E-cadherin表达显著下降,Vim-entin和N-cadherin表达显著升高(P<0.05).同时,缺氧条件下肝癌细胞迁移和侵袭能力显著增强(P<0.05).缺氧可导致HepG2、SMMC-7721停滞于静止期(G0/G1)的细胞数显著增多,缺氧条件下肝癌细胞对cisplatin耐药性显著增加(P<0.05);缺氧条件下ABCG2蛋白表达增加(P<0.05).[结论]缺氧能诱导肝癌细胞EMT转化而致侵袭转移,同时可导致对cisplatin耐药.“,”[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 hy-poxia model was established by using HepG2 and SMMC-7721 cells.The morphological changes were observed by in-verted 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 West-ern 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 expres-sion 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.