Bufalin targeting BFAR inhibits the occurrence and metastasis of gastric cancer through PI3K/AKT/mTOR signal pathway

Gastric Cancer (GC) is the most common malignant tumor of digestive system. Bufalin extracted from Venenum Bufonis is one of the most effective Anticancer monomers, which has been proved to play Anticancer roles in a variety of cancers such as ovarian Cancer, prostate Cancer and neuroblastoma. However, there are few studies on bufalin in GC, and lack of clear targets. The effect of bufalin on the proliferation and migration of GC cells was detected by CCK-8, scratch wound healing assay, transwell assay and Western blotting. The potential direct interaction proteins of bufalin were screened by human proteome microarray containing 21,838 human proteins. The target protein was determined by bioinformatics, and the binding sites were predicted by molecular docking technique. Biological experiments in vitro and in vivo were conducted to verify the effect of bufalin directly interaction protein and the mechanism of bufalin targeting the protein to inhibit the development of GC. The results showed that bufalin inhibited the proliferation and migration of MKN-45 and HGC-27 GC cell lines in vitro. BFAR, a direct interaction protein of bufalin has several potential binding sites to bufalin. BFAR is highly expressed in GC and promotes the occurrence and metastasis of GC by activating PI3K/Akt/mTOR signal pathway in vitro and in vivo. Bufalin reversed the promoting effect of BFAR on the carcinogenesis and metastasis of GC by down-regulating the expression of BFAR. Our results show that bufalin targeting BFAR inhibits the occurrence and metastasis of GC through PI3K/Akt/mTOR signal pathway. These results provide a new basis for bufalin as a promising drug for the treatment of GC.

BFAR; Bufalin; Gastric cancer; Metastasis; PI3K/AKT/mTOR signal pathway.