Synergistic anticancer effects of bufalin and sorafenib by regulating apoptosis associated proteins.
Synergistic anticancer effects of bufalin and sorafenib by regulating apoptosis associated proteins.
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蟾蜍灵和索拉非尼通过调节凋亡相关蛋白的协同抗癌作用
DOI：
10.3892/mmr.2018.8927
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发表时间：
2018-06
影响因子：
3.4
通讯作者：
Meng Z
中科院分区：
文献类型：
--
作者：
Wang H;Zhang C;Chi H;Meng Z
索拉非尼是目前公认的治疗肝细胞癌（HCC）的药物之一，但其抗肿瘤作用仍有待提高。蟾毒灵在HCC中显示出抗肿瘤作用；然而，两者联合治疗是否会产生增强的抗肿瘤效果尚不清楚。因此，在本研究中，我们研究了它们对HCC增殖和凋亡的联合作用。结果表明，蟾毒灵和索拉非尼在孵育24 h后均能抑制PLC/PRF/5和SMMC-7721细胞的增殖，并呈浓度依赖性，两种药物联合作用后抑制作用增强。在20 nM蟾毒灵和10µM索拉非尼处理的HCC细胞中，协同作用达到峰值。此外，细胞周期和末端脱氧核苷酸转移酶dUTP镍端标记实验显示，蟾毒灵也增强了索拉非尼诱导的细胞凋亡。集落形成试验表明，与单独治疗相比，联合治疗可显著抑制HCC增殖。此外，联合治疗后，b细胞淋巴瘤2相关X蛋白、caspase 7和多（腺苷二磷酸核糖）聚合酶在HCC细胞中上调。综上所述，本研究结果显示索拉非尼联合蟾毒灵治疗可协同抑制HCC增殖并诱导细胞凋亡。因此，蟾毒灵联合索拉非尼可能是HCC患者较好的治疗策略。
As one of the most recognized and well-known drugs for hepatocellular carcinoma (HCC), the antitumor effect of sorafenib against HCC remains to be improved. Bufalin has displayed an antitumor effect in HCC; however, whether the enhanced antitumor effect may be generated with their combined treatment remains unclear. Therefore, in the present study, their combined effects on HCC proliferation and apoptosis were investigated. It was revealed that either bufalin or sorafenib suppressed PLC/PRF/5 and SMMC-7721 cell proliferation in a concentration-dependent manner following incubation for 24 h, and the inhibitory effect was augmented with their combined treatment. The synergistic effect peaked in HCC cells treated with 20 nM bufalin and 10 µM sorafenib. In addition, cell cycle and terminal deoxynucleotidyl transferase dUTP nick-end labelling assays revealed that bufalin also enhanced sorafenib-induced apoptosis. Colony formation assay demonstrated that combined treatment significantly suppressed HCC proliferation compared with treatment with either of them alone. Furthermore, B-cell lymphoma 2-associated X protein, caspase 7 and poly-(adenosine diphosphate-ribose) polymerase were upregulated in HCC cells with combined treatment. Taken together, the results of the present study revealed that the treatment of sorafenib combined with bufalin synergistically suppressed HCC proliferation and induced apoptosis. Therefore, bufalin combined with sorafenib may be a favorable treatment strategy for patients with HCC.
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影响因子：
158.5
作者：
Llovet, Josep M.;Ricci, Sergio;Bruix, Jordi
通讯作者：
Bruix, Jordi
DOI：
10.1016/j.mrfmmm.2011.09.010
发表时间：
2012-04-01
影响因子：
2.3
作者：
Huang, Wen-Wen;Yang, Jai-Sing;Chung, Jing-Gung
通讯作者：
Chung, Jing-Gung
影响因子：
11.2
作者：
Liu, Li;Cao, Yichen;Carter, Christopher
通讯作者：
Carter, Christopher
影响因子：
3
作者：
Chang, Yong S.;Adnane, Jalila;Wilhelm, Scott
通讯作者：
Wilhelm, Scott
影响因子：
10.3
作者：
Carlomagno, F;Anaganti, S;Santoro, M
通讯作者：
Santoro, M