Chiu Chien-Ming, Huang Sung-Ying, Chang Shu-Fang, Liao Kuan-Fu, Chiu Sheng-Chun
Division of Colorectal Surgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan.
Department of Ophthalmology, Hsinchu Mackay Memorial Hospital, Hsinchu, Taiwan.
Onco Targets Ther. 2018 Mar 29;11:1777-1785. doi: 10.2147/OTT.S161534. eCollection 2018.
Hepatocellular carcinoma (HCC) is the most common form of hepatic malignancy in the world. We aimed to determine the effect of tanshinone IIA (Tan-IIA) in combination with sorafenib or its derivative SC-1 on cytotoxicity, apoptosis, and metastasis in human HCC cells.
Cytotoxicity was detected by MTT assay. Apoptosis and sub-G1 populations were analyzed by flow cytometry. Cell migration and invasion were evaluated by Transwell assay. Protein expression was detected by Western blot.
Tan-IIA combined with sorafenib or SC-1 exerted synergistic cytotoxicity in HCC cells. Elevated proportions of sub-G1 and caspase activation were observed in the combinative treatments; in addition, marked inhibition of cell migration and invasion, which could be mediated by the modulation of epithelial-mesenchymal transition was observed. pSTAT3 levels were significantly reduced as well.
A combination therapy using Tan-IIA and sorafenib or SC-1 could be a promising approach to target HCC, and further preclinical investigations are warranted to establish their synergetic advantage.
肝细胞癌(HCC)是全球最常见的肝脏恶性肿瘤形式。我们旨在确定丹参酮IIA(Tan-IIA)与索拉非尼或其衍生物SC-1联合使用对人肝癌细胞的细胞毒性、凋亡和转移的影响。
通过MTT法检测细胞毒性。通过流式细胞术分析凋亡和亚G1期细胞群。通过Transwell法评估细胞迁移和侵袭。通过蛋白质印迹法检测蛋白质表达。
Tan-IIA与索拉非尼或SC-1联合使用在肝癌细胞中发挥协同细胞毒性作用。在联合治疗中观察到亚G1期细胞比例升高和半胱天冬酶激活;此外,观察到细胞迁移和侵袭受到明显抑制,这可能是由上皮-间质转化的调节介导的。pSTAT3水平也显著降低。
使用Tan-IIA和索拉非尼或SC-1的联合疗法可能是靶向肝癌的一种有前景的方法,有必要进行进一步的临床前研究以确定它们的协同优势。