Jin Jin, Zhao Yujia, Guo Wan, Wang Bingrong, Wang Yigang, Liu Xinyuan, Xu Chuanlian
College of Life Sciences, Zhejiang Sci-Tech University, Xiasha Higher Education Zone, Hangzhou, 310018, Zhejiang Province, China.
Xinyuan Institute of Medicine and Biotechnology, College of Life Sciences, Zhejiang Sci-Tech University, No. 2 Road Xiasha District, Hangzhou, 310018, China.
Cytotechnology. 2019 Feb;71(1):401-409. doi: 10.1007/s10616-019-00301-w. Epub 2019 Jan 28.
Thiocoraline, a depsipeptide bisintercalator with potent antitumor activity, was first isolated from marine actinomycete Micromonospora marina. It possesses an intense toxicity to MCF-7 cells at nanomolar concentrations in a dose-dependent manner evaluated by MTT assay and crystal violet staining. We established a human breast thiocoraline-resistant cancer subline of MCF-7/thiocoraline (MCF-7/T) to investigate the expression variation of breast cancer resistance proteins (BCRP) and its subsequent influence on drug resistance. Colony-forming assay showed that the MCF-7 cells proliferated faster than the MCF-7/T cells in vitro. Western blot analysis demonstrated that thiocoraline increased the phosphorylation of Akt. Additionally, the sensitivity of tumor cells to thiocoraline was reduced with a concurrent rise in phosphorylation level of Akt and of BCRP expression.These studies indicated that thiocoraline probably mediated the drug resistance via PI3K/Akt/BCRP signaling pathway. MK-2206 dihydrochloride, a selective phosphorylation inhibitor of Akt, significantly decreased MCF-7 cell viability under exposure to thiocoraline compared to the control. However, it was not obviously able to decrease MCF-7/T cell viability when cells were exposed to thiocoraline.
硫代珊瑚素是一种具有强大抗肿瘤活性的缩肽双嵌入剂，最初从海洋放线菌滨海小单孢菌中分离得到。通过MTT法和结晶紫染色评估，它在纳摩尔浓度下对MCF-7细胞具有强烈的毒性，且呈剂量依赖性。我们建立了人乳腺癌硫代珊瑚素耐药细胞亚系MCF-7/硫代珊瑚素（MCF-7/T），以研究乳腺癌耐药蛋白（BCRP）的表达变化及其对耐药性的后续影响。集落形成试验表明，MCF-7细胞在体外比MCF-7/T细胞增殖更快。蛋白质免疫印迹分析表明，硫代珊瑚素增加了Akt的磷酸化。此外，随着Akt磷酸化水平和BCRP表达的同时升高，肿瘤细胞对硫代珊瑚素的敏感性降低。这些研究表明，硫代珊瑚素可能通过PI3K/Akt/BCRP信号通路介导耐药性。Akt的选择性磷酸化抑制剂盐酸MK-2206，与对照组相比，在硫代珊瑚素作用下显著降低了MCF-7细胞的活力。然而，当细胞暴露于硫代珊瑚素时，它并不能明显降低MCF-7/T细胞的活力。
