Podofilox suppresses gastric cancer cell proliferation by regulating cell cycle arrest and the c‑Myc/ATG10 axis

An,Juan; Liu,Yan; Duo,Shenglan; Ma,Xiaoming; An,Ling; Yan,Yunfei; Ji,Dongde; Yan,Yupeng; Cheng,Qiliang; Su,Zhanhai

doi:10.3892/etm.2021.10637

Podofilox suppresses gastric cancer cell proliferation by regulating cell cycle arrest and the c‑Myc/ATG10 axis

Authors:
- Juan An
- Yan Liu
- Shenglan Duo
- Xiaoming Ma
- Ling An
- Yunfei Yan
- Dongde Ji
- Yupeng Yan
- Qiliang Cheng
- Zhanhai Su
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Affiliations: Department of Basic Medical Sciences, Qinghai University Medical College, Xining, Qinghai 810016, P.R. China, Department of Doppler Ultrasound, Qinghai Red Cross Hospital, Xining, Qinghai 810099, P.R. China, Department of Gastrointestinal Tumor Surgery, The Affiliated Hospital of Qinghai University, Xining, Qinghai 810012, P.R. China, Department of Internal Medicine, Qinghai People's Hospital, Xining, Qinghai 810007, P.R. China
Published online on: August 23, 2021 https://doi.org/10.3892/etm.2021.10637
Article Number: 1203
Copyright: © An et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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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