Anti-tumor activity of butorphanol in colorectal cancer via targeting SIGMAR1

Discov Oncol. 2024 Nov 26;15(1):711. doi: 10.1007/s12672-024-01581-1.

Abstract

Colorectal cancer (CRC) stands for a prevailing gastrointestinal neoplasm, concomitant with considerable occurrence and lethality rate. Butorphanol, a synthetic opioid analgesic medication targeting the opiate receptor, has been recently reckoned to harbor anti-oncogenic properties. This study proposes to delineate the impacts of butorphanol on CRC and the interrelated response mechanism. In sigma non-opioid intracellular receptor 1 (SIGMAR1)-overexpressing CRC cells treated by varying concentrations of butorphanol, the functional experiments including CCK-8 method, EDU staining, wound healing and transwell assays severally appraised the capabilities for CRC cells to proliferate, migrate as well as invade. TUNEL staining assayed the cellular apoptotic level. The expressions of proteins implicated in proliferation, metastasis as well as apoptosis were ascertained by Western blot. CB-Dock2 server predicated butorphanol-SIGMAR1 interaction and Western blot also examined SIGMAR1 expression. Noticeably, butorphanol profoundly eliminated the capabilities of CRC cells to proliferate, migrate and invade whilst intensified the cellular apoptotic level with the ascending doses. Butorphanol was identified to possess an interrelation with SIGMAR1 and concentration-dependently lowered SIGMAR1 expression. Elevation of SIGMAR1 partially blunted the affection of butorphanol on the biological events of CRC cells. To sum up, butorphanol may extenuate the aggressive cellular behaviors to produce tumor-suppressing activity on CRC via binding with SIGMAR1.

Keywords: Apoptosis; Butorphanol; Colorectal cancer; In vitro; Metastasis; Sigma non-opioid intracellular receptor 1.