An Juan, Liu Yan, Duo Shenglan, Ma Xiaoming, An Ling, Yan Yunfei, Ji Dongde, Yan Yupeng, Cheng Qiliang, Su Zhanhai
Department of Basic Medical Sciences, Qinghai University Medical College, Xining, Qinghai 810016, P.R. China.
State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining, Qinghai 810016, P.R. China.
Exp Ther Med. 2021 Nov;22(5):1203. doi: 10.3892/etm.2021.10637. Epub 2021 Aug 23.
Gastric cancer (GC) is a malignancy for which effective therapeutic drugs are limited. Podofilox exhibits antitumor effects in various types of cancer; however, whether it may inhibit GC growth remains unknown. The aim of the present study was to investigate the role of podofilox in GC. Cell Counting Kit-8, colony formation and cell cycle assays were used to detect the role of podofilox on cellular proliferation and the cell cycle, respectively. A microarray was used to detect the transcriptional changes induced by podofilox in GC cells. The results of the present study demonstrated that podofilox inhibited GC cell proliferation and colony formation. The half maximal inhibitory concentration of podofilox in AGS and HGC-27 cells was 2.327 and 1.981 nM, respectively. In addition, treatment with podofilox induced G/G cell cycle arrest. Molecular analysis based on microarray data demonstrated that podofilox altered the expression levels of genes involved in the cell cycle, c-Myc and p53 signaling. Autophagy-related 10 (ATG10), which was highly expressed in GC tissues, was also downregulated by podofilox, as demonstrated by the results of the microarray analysis and immunoblotting. To determine the involvement of ATG10 in GC, ATG10 was knocked down in GC cells by small interfering RNA, which suppressed the proliferation and colony formation of GC cells compared with those observed in the control-transfected cells. Taken together, the results of the present study suggested that podofilox may inhibit GC cell proliferation by preventing the cell cycle progression and regulating the c-Myc/ATG10 signaling pathway.
胃癌（GC）是一种有效治疗药物有限的恶性肿瘤。鬼臼毒素在多种癌症类型中表现出抗肿瘤作用；然而，它是否能抑制胃癌生长仍不清楚。本研究的目的是探讨鬼臼毒素在胃癌中的作用。分别使用细胞计数试剂盒-8、集落形成和细胞周期分析来检测鬼臼毒素对细胞增殖和细胞周期的作用。利用微阵列检测鬼臼毒素在胃癌细胞中诱导的转录变化。本研究结果表明，鬼臼毒素抑制胃癌细胞增殖和集落形成。鬼臼毒素在AGS和HGC-27细胞中的半数最大抑制浓度分别为2.327 nM和1.981 nM。此外，鬼臼毒素处理诱导G/G细胞周期阻滞。基于微阵列数据的分子分析表明，鬼臼毒素改变了参与细胞周期、c-Myc和p53信号通路的基因表达水平。微阵列分析和免疫印迹结果显示，在胃癌组织中高表达的自噬相关蛋白10（ATG10）也被鬼臼毒素下调。为了确定ATG10在胃癌中的作用，通过小干扰RNA在胃癌细胞中敲低ATG10，与对照转染细胞相比，这抑制了胃癌细胞的增殖和集落形成。综上所述，本研究结果表明，鬼臼毒素可能通过阻止细胞周期进程和调节c-Myc/ATG10信号通路来抑制胃癌细胞增殖。
