Meloxicam combined with sorafenib synergistically inhibits tumor growth of human hepatocellular carcinoma cells via ER stress-related apoptosis.
Meloxicam combined with sorafenib synergistically inhibits tumor growth of human hepatocellular carcinoma cells via ER stress-related apoptosis.
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美洛昔康联合索拉非尼通过内质网应激相关的细胞凋亡协同抑制人肝癌细胞的肿瘤生长。
DOI：
10.3892/or.2015.4181
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发表时间：
2015-10
期刊：
影响因子：
4.2
通讯作者：
李杰
中科院分区：
文献类型：
--
作者：
Zhong J;Xiu P;李杰
索拉非尼（SOR）是晚期肝细胞癌（HCC）的有前途的治疗方法。但是，尚未完全探索毒性和耐药性的确切机制，HCC治疗迫切需要新的策略。 Meloxicam（Mel）是
Sorafenib (SOR) is a promising treatment for advanced hepatocellular carcinoma (HCC). However, the precise mechanisms of toxicity and drug resistance have not been fully explored and new strategies are urgently needed for HCC therapy. Meloxicam (MEL) is a selective cyclooxygenase-2 (COX-2) inhibitor which elicits antitumor effects in human HCC cells. In the present study, we investigated the interaction between MEL and SOR in human SMMC‑7721 cells and the role endoplasmic reticulum (ER) stress exerts in the combination of SOR with MEL treatment-induced cytotoxicity. Our results revealed that the combination treatment synergistically inhibited cell proliferation and enhanced apoptosis. Furthermore, the combination treatment enhanced ER stress-related molecules which involved in SMMC-7721 cell apoptosis. GRP78 knockdown by siRNA or co-treatment with MG132 significantly increased this combination treatment-induced apoptosis. In addition, we found that the combination treatment suppressed tumor growth by way of activation of ER stress in in vivo models. We concluded that the combination of SOR with MEL treatment-induced ER stress, and eventually apoptosis in human SMMC-7721 cells. Knockdown of GRP78 using siRNA or proteosome inhibitor enhanced the cytotoxicity of the combination of SOR with MEL-treatment in SMMC-7721 cells. These findings provided a new potential treatment strategy against HCC.
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影响因子：
21.3
作者：
Tabas, Ira;Ron, David
通讯作者：
Ron, David
影响因子：
5.2
作者：
Komatsu S;Miyazawa K;Moriya S;Takase A;Naito M;Inazu M;Kohno N;Itoh M;Tomoda A
通讯作者：
Tomoda A
影响因子：
5.2
作者：
Lönnroth C;Andersson M;Asting AG;Nordgren S;Lundholm K
通讯作者：
Lundholm K
影响因子：
158.5
作者：
Llovet, Josep M.;Ricci, Sergio;Bruix, Jordi
通讯作者：
Bruix, Jordi
影响因子：
11.2
作者：
Wilhelm, SM;Carter, C;Trail, PA
通讯作者：
Trail, PA