Rafoxanide promotes apoptosis and autophagy of gastric cancer cells by suppressing PI3K /Akt/mTOR pathway

Rafoxanide is commonly used as anti-helminthic medicine in veterinary medicine, a main compound of salicylanilide. Previous studies have reported that rafoxanide, as an inhibitor of BRAF V600E mutant protein, inhibits the growth of colorectal cancer, multiple myeloma, and skin cancer. However, its t...

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Bibliographic Details
Published in:Experimental cell research 2019-12, Vol.385 (2), p.111691-111691, Article 111691
Main Authors: Liu, Jia-Zhou, Hu, Yi-Lin, Feng, Ying, Guo, Yi-Bing, Liu, Yi-Fei, Yang, Jun-Ling, Mao, Qin-Sheng, Xue, Wan-Jiang
Format: Article
Language:English
Subjects:
Apoptosis
Autophagy
Gastric cancer
PI3K
Rafoxanide
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Summary:Rafoxanide is commonly used as anti-helminthic medicine in veterinary medicine, a main compound of salicylanilide. Previous studies have reported that rafoxanide, as an inhibitor of BRAF V600E mutant protein, inhibits the growth of colorectal cancer, multiple myeloma, and skin cancer. However, its therapeutic effect on gastric cancer (GC) and the potential mechanism has not been investigated. Here, we have found that rafoxanide inhibited the proliferation of GC cells in vitro, arrested the cell cycle in the G0/G1 phase, and promoted apoptosis and autophagy in GC cells. Treatment with specific autophagy inhibitor 3-methyladenine drastically inhibited the apoptotic cell death effect by suppressing the switch from autophagy to apoptosis. Mechanistically, we found that rafoxanide inhibited the growth of GC cells in vitro by inhibiting the activity of the PI3K/Akt/mTOR signaling pathway. This process induced autophagy, which essentially resulted in the apoptosis of GC cells. Results from subcutaneous implanted tumor models in nude mice also indicated that rafoxanide inhibited the growth of GC cells in vivo. Taken together, our findings revealed that rafoxanide inhibited the growth of GC cells both in vitro and vivo, indicating a potential drug candidate for the treatment of GC. [Display omitted] •Rafoxanide has the ability to inhibit tumor growth in vitro and in vivo.•Rafoxanide has no apparent toxic effect on normal cells and major organs of nude mice.•Rafoxanide inhibits the activation of the PI3K/Akt signaling pathway, then decreased phospho-mTOR levels.
ISSN:0014-4827
1090-2422
DOI:10.1016/j.yexcr.2019.111691