Podofilox suppresses gastric cancer cell proliferation by regulating cell cycle arrest and the c-Myc/ATG10 axis.
Podofilox suppresses gastric cancer cell proliferation by regulating cell cycle arrest and the c-Myc/ATG10 axis.
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DOI：
10.3892/etm.2021.10637
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发表时间：
2021-11
影响因子：
2.7
通讯作者：
Su Z
中科院分区：
文献类型：
--
作者：
An J;Liu Y;Duo S;Ma X;An L;Yan Y;Ji D;Yan Y;Cheng Q;Su Z
胃癌（GC）是一种恶性肿瘤，其有效的治疗药物有限. Podofilox在各种类型的癌症中表现出抗肿瘤作用;然而，它是否可以抑制GC生长仍然未知。本研究的目的是探讨podofilox在GC中的作用。细胞计数试剂盒-8、集落形成实验和细胞周期实验分别检测podofilox对细胞增殖和细胞周期的影响。用基因芯片检测podofilox诱导的胃癌细胞转录水平的变化。本研究的结果表明，podofilox抑制GC细胞增殖和集落形成。podofilox在AGS和HGC-27细胞中的半数最大抑制浓度分别为2.327和1.981 nM。此外，用podofilox处理诱导G 0/G1细胞周期停滞。基于微阵列数据的分子分析表明，podofilox改变了参与细胞周期、c-Myc和p53信号传导的基因的表达水平。自噬相关10（ATG 10），这是高表达的GC组织，也下调podofilox，如芯片分析和免疫印迹的结果表明。为了确定ATG 10在GC中的参与，ATG 10在GC细胞中被小干扰RNA敲低，与在对照转染细胞中观察到的那些相比，其抑制GC细胞的增殖和集落形成。综上所述，本研究的结果表明，podofilox可能通过阻止细胞周期进程和调节c-Myc/ATG 10信号通路来抑制GC细胞增殖。
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 G0/G1 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.
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影响因子：
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作者：
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DOI：
10.3390/v8100295
发表时间：
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期刊：
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影响因子：
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作者：
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通讯作者：
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