Bufalin inhibits peritoneal dissemination of gastric cancer through endothelial nitric oxide synthase-mitogen-activated protein kinases signaling pathway.

Dan Zou, Jincheng Song, Mingming Deng, Yanju Ma, Chunjiao Yang, Jiaqing Liu, Song Wang, Zhenpeng Wen, Yu Tang, Xiujuan Qu, Ye Zhang

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2021 May

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Peritoneal dissemination threatens the survival of patients with gastric cancer (GC). Bufalin is an extract of traditional Chinese medicine, which has been proved to have anticancer effect. The target of bufalin in suppressing gastric cancer peritoneal dissemination (GCPD) and the underlying mechanism are still unclear. In this research, GC cell line MGC-803 and high-potential peritoneal dissemination cell line MKN-45P were treated with bufalin or L-NAME. Malignant biological behavior and protein level of GC cell lines were detected with MTT, wound healing, transwell, adhesion, and western blotting. Bioinformatics analysis and patient tissues were used to verify the role of endothelial nitric oxide synthase (NOS3) in GC. Mice model was used to assess the effect of bufalin and role of NOS3 in vivo. We found that bufalin inhibited the proliferation, invasion, and migration in GC cell lines. NOS3, which was an independent prognostic factor of GC patients, was predicted to be a potential target of bufalin. Further experiments proved that bufalin reduced the phosphorylation of NOS3, thereby inhibiting the mitogen-activated protein kinase (MAPK) signaling pathway, and ultimately suppressed GCPD by inhibiting EMT process. In conclusion, NOS3 was a potential therapeutic target and prognostic biomarker of GC. Bufalin could suppress GCPD through NOS3-MAPK signaling pathway, which provided more evidence support for intraperitoneal perfusion of bufalin to treat GCPD. © 2021 Federation of American Societies for Experimental Biology.

Citation

Dan Zou, Jincheng Song, Mingming Deng, Yanju Ma, Chunjiao Yang, Jiaqing Liu, Song Wang, Zhenpeng Wen, Yu Tang, Xiujuan Qu, Ye Zhang. Bufalin inhibits peritoneal dissemination of gastric cancer through endothelial nitric oxide synthase-mitogen-activated protein kinases signaling pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2021 May;35(5):e21601