Ding Kun, Fan Lu, Chen Shijun, Wang Yanna, Yu Haifeng, Sun Yanni, Yu Jiguang, Wang Li, Liu Xiangzhong, Liu Youde
Department of Liver Diseases, Jinan Infectious Disease Hospital, Shandong University School of Medicine, Jian, Shandong 250000, P.R. China.
Yantai Infectious Disease Hospital, Yantai, Shandong 264001, P.R. China.
Oncol Rep. 2015 Dec;34(6):3297-303. doi: 10.3892/or.2015.4306. Epub 2015 Sep 23.
Osteopontin (OPN) is a multi-functional cytokine involved in cell survival, migration and adhesion. Increasing evidence has elucidated its role in tumorigenesis, progression and metastasis. However, the role of OPN in chemoresistance of human hepatocellular carcinoma (HCC) has not yet been clarified. In the present study, we examined the expression of OPN in human HCC samples before and after cisplatin-treatment, the results showed that OPN was significantly increased in cisplatin-resistant specimens. We then studied the effect of cisplatin on OPN expression in HCC cells, after exposure to cisplatin, the expression of OPN in HCC cells was elevated compared to control cells. We also found that PI3K/AKT signaling pathway was also activated by cisplatin and this effect was induced by the OPN pathway. To study the effect of OPN on chemoresistance, HCC cells were treated with cisplatin along with OPN. Incubation with OPN enchanced the chemoresistance of HCC cells to cisplatin. In contrast, blockage of OPN pathway promoted the chemosensitivity of HCC cells to cisplatin. Our results suggest that OPN enhanced chemoresistance of cisplatin in HCC cells by activating PI3K/AKT signaling pathway, blocking the OPN pathway might be a novel way to overcome the disease.
骨桥蛋白（OPN）是一种多功能细胞因子，参与细胞存活、迁移和黏附。越来越多的证据阐明了其在肿瘤发生、进展和转移中的作用。然而，OPN在人类肝细胞癌（HCC）化疗耐药中的作用尚未明确。在本研究中，我们检测了顺铂治疗前后人类HCC样本中OPN的表达，结果显示顺铂耐药标本中OPN显著增加。然后我们研究了顺铂对HCC细胞中OPN表达的影响，暴露于顺铂后，HCC细胞中OPN的表达相对于对照细胞升高。我们还发现PI3K/AKT信号通路也被顺铂激活，且这种作用是由OPN通路诱导的。为了研究OPN对化疗耐药的影响，HCC细胞用顺铂和OPN共同处理。与OPN孵育增强了HCC细胞对顺铂的化疗耐药性。相反，阻断OPN通路促进了HCC细胞对顺铂的化疗敏感性。我们的结果表明，OPN通过激活PI3K/AKT信号通路增强了HCC细胞对顺铂的化疗耐药性，阻断OPN通路可能是克服该疾病的一种新方法。
