Ma Jun Li, Zeng Shan, Zhang Yan, Deng Gan Lu, Shen Hong
Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China, 410008.
Tumour Biol. 2016 May;37(5):6177-84. doi: 10.1007/s13277-015-4458-z. Epub 2015 Nov 27.
Drug resistance is one characteristic of hepatocellular carcinoma (HCC) and can affect the prognosis of patients directly. To explore drug resistance well, we established an oxaliplatin (OXA)-resistant cell line Bel-7402/OXA by exposure to gradually increased concentration of OXA. Some biological characters, such as proliferation, migration, and invasion, were studied. Drug sensitivity and the mechanisms of drug resistance were also investigated. We found that the resistant index of Bel-7402/OXA was 8.3. In comparison with Bel-7402, the percentages of cells in S and G2/M phase were increased. The nature apoptosis rate and drug-after apoptosis rate were all decreased in Bel-7402/OXA, as compared to Bel-7402. Bel-7402/OXA acquired increased migration and invasion ability with epithelial-mesenchymal transition (EMT) phenotype. Knockdown of EMT transcription factor Snail could reverse EMT and sensitized Bel-7402/OXA cells to OXA. EMT was one mechanism of drug resistance and may be a novel target of treatment for drug resistance.
耐药性是肝细胞癌（HCC）的一个特征，可直接影响患者的预后。为了深入探究耐药性，我们通过逐步增加奥沙利铂（OXA）的浓度，建立了奥沙利铂耐药细胞系Bel-7402/OXA。研究了其一些生物学特性，如增殖、迁移和侵袭。还研究了药物敏感性和耐药机制。我们发现Bel-7402/OXA的耐药指数为8.3。与Bel-7402相比，S期和G2/M期细胞的百分比增加。与Bel-7402相比，Bel-7402/OXA的自然凋亡率和药物诱导后的凋亡率均降低。Bel-7402/OXA获得了增强的迁移和侵袭能力，并具有上皮-间质转化（EMT）表型。敲低EMT转录因子Snail可逆转EMT，并使Bel-7402/OXA细胞对OXA敏感。EMT是耐药的一种机制，可能是耐药治疗的一个新靶点。
