Zhang Bei, Wang Xueya, Cai Fengfeng, Chen Weijie, Loesch Uli, Bitzer Johannes, Zhong Xiao Yan
Laboratory for Gynecologic Oncology, Women's Hospital/Department of Biomedicine, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland.
Tumour Biol. 2012 Dec;33(6):1855-62. doi: 10.1007/s13277-012-0445-9. Epub 2012 Jul 7.
This study investigated the anticancer effect and mechanism of salinomycin, a selective inhibitor of cancer stem cell, on human ovarian cancer cell line OV2008 in vitro and in vivo. The growth inhibitory effect of salinomycin on ovarian cancer cell line OV2008 was determined by measuring cell viability using the resazurin reduction assay. Apoptotic nuclear morphology was visualized by 4,6-diamino-2-phenylindole staining technique. The percentages of apoptotic cells and cell cycle parameters were detected by flow cytometry. The activity of p38 mitogen-activated protein kinase (p38 MAPK) was analyzed by Bio-Plex phosphoprotein assay. In vivo activity of salinomycin was assayed through tumor growth. Salinomycin caused concentration- (0.01-200 μM) and time-dependent (24-72 h) growth inhibitory effects in OV2008. Cell nuclear morphology observations showed that salinomycin-treated OV2008 cells displayed typical apoptotic characteristics. Salinomycin significantly increased the percentages of apoptotic cells in OV2008, showing a concentration- and time-dependent manner. There was no cell cycle arrest in the G1/G0, S, and G2/M phases between salinomycin-treated cells and control cells. Salinomycin also enhanced the phosphorylation of p38 MAPK. Moreover, salinomycin significantly inhibited the growth of the ovarian xenograft tumors. Salinomycin exhibited significant growth inhibition and induction of apoptosis in the human ovarian cancer cell line OV2008. The data suggested that salinomycin-induced apoptosis in OV2008 might be associated with activating p38 MAPK and merits further investigations.
本研究在体外和体内研究了癌症干细胞的选择性抑制剂沙林霉素对人卵巢癌细胞系OV2008的抗癌作用及其机制。采用刃天青还原试验通过测量细胞活力来确定沙林霉素对卵巢癌细胞系OV2008的生长抑制作用。通过4,6-二脒基-2-苯基吲哚染色技术观察凋亡细胞核形态。通过流式细胞术检测凋亡细胞百分比和细胞周期参数。采用生物芯片磷蛋白分析方法分析p38丝裂原活化蛋白激酶（p38 MAPK）的活性。通过肿瘤生长情况测定沙林霉素的体内活性。沙林霉素对OV2008产生浓度依赖性（0.01 - 200 μM）和时间依赖性（24 - 72小时）的生长抑制作用。细胞核形态观察显示，经沙林霉素处理的OV2008细胞呈现典型的凋亡特征。沙林霉素显著增加了OV2008中凋亡细胞的百分比，呈浓度和时间依赖性。经沙林霉素处理的细胞与对照细胞之间在G1/G0、S和G2/M期均未出现细胞周期阻滞。沙林霉素还增强了p38 MAPK的磷酸化。此外，沙林霉素显著抑制了卵巢异种移植肿瘤的生长。沙林霉素对人卵巢癌细胞系OV2008具有显著的生长抑制作用并诱导凋亡。数据表明，沙林霉素诱导OV2008细胞凋亡可能与激活p38 MAPK有关，值得进一步研究。
