上皮细胞粘附分子在肝动脉化疗栓塞治疗肝癌中的表达改变及其功能

目的明确肝动脉化疗栓塞(transcatheter hepatic arterial chemoembolization,TACE)治疗对肝细胞癌(hepatocellular carcinoma,HCC)肿瘤组织中肿瘤干细胞指示分子——上皮细胞粘附分子(epithelial cell adhesion molecule,Ep CAM)表达及肝癌干细胞生物学行为的影响。方法用实时PCR分别检测30例经TACE治疗和30例未经TACE治疗的HCC患者肿瘤组织中Ep CAM的表达水平。在此基础上,用Ep CAM的si RNA载体,在HCC细胞系Hep G2和高侵袭性的MHCC-97H中检测Ep CAM对抗肿瘤药物作用的影响;在MHCC-97H细胞系中,检测降低Ep CAM表达对MHCC-97H侵袭作用的影响。结果接受TACE治疗的HCC患者肿瘤组织中的Ep CAM表达水平升高(P0.05)。与对照组相比,在Hep G2细胞中转染Ep CAM的si RNA能够显著上调Hep G2细胞对分子靶向抗肿瘤药物索拉非尼以及细胞毒性化疗药物奥沙利铂和表柔比星的敏感性。在MHCC-97H中转染Ep CAM的si RNA能够显著抑制其侵袭作用。结论 TACE治疗可引起HCC组织中Ep CAM的表达水平明显升高;降低HCC细胞中Ep CAM表达水平,可导致HCC细胞的肿瘤干细胞特征如侵袭性显著下降,对抗肿瘤药物的敏感性升高。

The influence and alteration of EpCAM expression in TACE treated hepatocellular carcinoma

ObjectiveTo determine whether transcatheter arterial chemoembolization (TACE) treatment modulates (cancer stem cell, CSC) marker expression and the detailed function of EpCAM in HCC cells via its siRNA.MethodsThe expression levels of EpCAM were detected by qPCR in 30 HCC patients with TACE treatment and 30 HCC patients without TACE treatment, respectively. On this basis, we detected the effect to anti-tumor agents action of EpCAM in HCC cell lines HepG2 and high invasive MHCC-97H by siRNA carrier of EpCAM. Next, the siRNA of EpCAM was transfected to determine whether EpCAM modulates HCC cells’in vitro invasion and the sensitivity to anti-tumor agents.ResultsEpCAM expression levels in tumor tissues of HCC patients treated with TACE were significantly higher (P<0.05).In contrast to the control group, Transfection of EpCAM siRNA enhanced the sensitivity of HepG2 to sorafenib, oxaliplatin and epirubicin. In addition, EpCAM siRNA also disrupted the invasion of MHCC-97H cells.ConclusionsTACE can increase EpCAM expression level in HCC significantly; Reduce of EpCAM expression levels in HCC cells can lead to HCC cells of tumor stem cell characteristics such as invasion significantly decreased, and increase sensitivity to chemotherapeutic drugs.