Opsin3 sensitizes hepatocellular carcinoma cells to 5-fluorouracil treatment by regulating the apoptotic pathway
Opsin3 sensitizes hepatocellular carcinoma cells to 5-fluorouracil treatment by regulating the apoptotic pathway
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Opsin3通过调节细胞凋亡途径使肝细胞癌细胞对5-氟尿嘧啶治疗敏感
DOI：
10.1016/j.canlet.2012.01.035
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发表时间：
2012-07-01
期刊：
影响因子：
9.7
通讯作者：
Zhu, Changliang
中科院分区：
文献类型：
--
作者：
Jiao, Jianhua;Hong, Shanchao;Zhu, Changliang
肝细胞癌（HCC）是全球第三大常见癌症，每年造成超过50万人死亡，其中约一半在中国。化疗是晚期HCC患者的最佳治疗方法，尽管化疗耐药性已成为成功抗癌治疗的重要障碍。视蛋白3（opsin 3，OPN 3），也称为脑视蛋白或全视蛋白，在5-氟尿嘧啶（5-FU）抗性的Bel 7402（5-FU）细胞中的表达低于5-FU敏感的Bel 7402细胞。为了探索OPN 3在5-FU抗性中的作用，产生OPN 3过表达（Bel 7402（5-FU）-OPN 3）和敲低（Bel 7402-RNAi-OPN 3）细胞系。Bel 7402（5-FU）-OPN 3细胞对5-FU处理的敏感性高于对照，而OPN 3敲低导致5-FU抗性显著增加。这一结果在第二个HCC细胞系HepG 2中得到了复制。进一步的机制研究表明，在Bel 7402（5-FU）细胞中，OPN 3水平降低通过增加磷酸化Akt和Bcl 2/Bax比值激活抗凋亡通路，而OPN 3过表达则使该通路失活。综上所述，这些结果表明，OPN 3耗竭参与5-FU耐药性，靶向OPN 3的治疗策略可能会提高HCC对化疗的敏感性。(C)2012爱思唯尔爱尔兰有限公司保留所有权利。
Hepatocellular carcinoma (HCC) is the third most common cancer worldwide, causing over 0.5 million deaths per year, with approximately half of these in China. Chemotherapy is the optimal treatment for patients with advanced HCC, although chemoresistance has become a significant obstacle to successful anti-cancer therapy. The expression of opsin3 (OPN3), also called encephalopsin or panopsin, is lower in 5-fluorouracil (5-FU)-resistant Bel7402(5-FU) cells compared to 5-FU-sensitive Bel7402 cells. To explore the role of OPN3 in 5-FU resistance, OPN3 overexpressing (Bel7402(5-FU)-OPN3) and knockdown (Bel7402-RNAi-OPN3) cell lines were generated. Bel7402(5-FU)-OPN3 cells were more sensitive to 5-FU treatment than controls, while OPN3 knockdown resulted in a significant increase in 5-FU resistance. This result was replicated in a second HCC cell line, HepG2. Further investigation of the mechanism revealed that decreased OPN3 levels in Bel7402(5-FU) cells activated the anti-apoptotic pathway through increasing phospho-Akt and the Bcl2/Bax ratio, while overexpression of OPN3 inactivated this pathway. Taken together, these results suggest that OPN3 depletion is involved in 5-FU resistance, and that therapeutic strategies targeting OPN3 may improve HCC sensitivity to chemotherapy. (C) 2012 Elsevier Ireland Ltd. All rights reserved.