体外化疗后残余肝癌细胞侵袭转移潜能变化及其机制

Changes of metastatic potentials of residual hepatocellular carcinoma cells after in vitro chemotherapy and the action mechanisms

目的探讨体外化疗后残余肝癌细胞侵袭转移潜能变化及其机制。方法以2mol／L奥沙利铂对人肝癌细胞株MHCC97L和HepG2进行体外冲击化疗，获得残癌细胞株MHCC97L-oxa和HepG2-oxa。对比研究残癌细胞株和母细胞株的侵袭、运动、增殖能力以及分子表型的差异。结果与母细胞株比较，MHCC97L-oxa和HepG2-oxa细胞显示出显著增强的运动能力（19．17±2．64比29．50±5．28，P〈0．01和12．33±2．73比21．17±3．13，P〈0．01）和侵袭能力（增强0．89倍，P〈0．01和增强1．58倍，P〈0．01），而增殖能力则显著下降。MHCC97L—oxa和HepG2．oxa细胞在形态和分子表型上明显区别于MHCC97L和HepG2，呈现出间质细胞形态，伴E-钙粘蛋白（E-cadherin）表达显著下调，N-cadherin、波形蛋白（vimentin）以及转录因子Snail表达显著增强，细胞呈现上皮-间质转化。结论体外化疗后残余肝癌细胞发生上皮-间质转化，侵袭转移潜能增强。

Objective To investigate the changes of biological features in the residual neoatocellular carcinoma （HCC） cells after in vitro chemotherapy and the action mechanisms. Methods Residual HCC cell lines MHCC97L-oxa and HepG2-oxa after chemotherapy were established by pulsed exposure of MHCC97L and HepG2 cells to 2 mol/L oxaliplatin in vitro. The changes of tumor cells in mobility, invasion, proliferation and molecular phenotype were compared between MHCC97L-oxa and MHCC97L cells, and HepG2-oxa and HepG2 cells. Results Compared with untreated MHCC97L and HepG2 cells, MHCC97L-oxa and HepG2-oxa cells showed enhanced motility （ 19. 17±2. 64 vs. 29. 50 ±5. 28 ,P 〈0. 01 and 12. 33±2. 73 vs. 21.17± 3.13,P 〈 0. 01 ） and increase invasion （0. 89 fold,P 〈 0. 01 and 1.58 fold, P 〈0. 01 ） and decreased proliferation. MHCC97L-oxa and HepG2-oxa cells were apparently different from their parent MHCC97L and HepG2 cells in appearance, demonstrating a mesenchymal-like cell appearance. Decreased expression of E-cadherin and increased expression of N-cadherin, vimentin and transcription factor Snail were detected in MHCC97L-oxa and HepG2 cells. Conclusion Residual HCC cells after oxaliplatin treatment underwent epithelial mesenchymal transition （EMT） and had enhanced metastatic potential.