Abstract:
: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.
journal_name
Exp Cell Resjournal_title
Experimental cell researchauthors
Liu JZ,Hu YL,Feng Y,Guo YB,Liu YF,Yang JL,Mao QS,Xue WJdoi
10.1016/j.yexcr.2019.111691subject
Has Abstractpub_date
2019-12-15 00:00:00pages
111691issue
2eissn
0014-4827issn
1090-2422pii
S0014-4827(19)30565-8journal_volume
385pub_type
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