Cyclovirobuxine D inhibits colorectal cancer tumorigenesis via the CTHRC1?AKT/ERK?Snail signaling pathway.

ABSTRACT: Cyclovirobuxine D (CVB?D) is an alkaloid, which is mainly derived from Buxus microphylla. It has been reported that CVB?D has positive effects on breast cancer, gastric cancer and other malignant tumors. However, to the best of our knowledge, there are no reports regarding the effects of CVB?D on colorectal cancer (CRC). The purpose of the present study was to determine the anticancer effects of CVB?D and further elucidate its molecular mechanism(s). DLD?1 and LoVo cell lines were selected to evaluate the antitumor effect of CVB?D. Cytotoxicity, viability and proliferation were evaluated by the MTT and colony formation assays. Flow cytometry was used to detect the effects on apoptosis and the cell cycle in CVB?D?treated CRC cells. The migration and invasion abilities of CRC cells were examined by wound healing and Transwell assays. In addition, RNA sequencing, bioinformatics analysis and western blotting were performed to investigate the target of drug action and clarify the molecular mechanisms. A xenograft model was established using nude mice, and ultrasound was employed to assess the preclinical therapeutic effects of CVB?D in vivo. It was identified that CVB?D inhibited the proliferation, migration, stemness, angiogenesis and epithelial?mesenchymal transition of CRC cells, and induced apoptosis and S?phase arrest. In addition, CVB?D significantly inhibited the growth of xenografts. It is notable that CVB?D exerted anticancer effects in CRC cells partly by targeting collagen triple helix repeat containing 1 (CTHRC1), which may be upstream of the AKT and ERK pathways. CVB?D exerted anticancer effects through the CTHRC1?AKT/ERK?Snail signaling pathway. Targeted therapy combining CTHRC1 with CVB?D may offer a promising novel therapeutic approach for CRC treatment.

SUBMITTER: Jiang F 

PROVIDER: S-EPMC7252468 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature