Butorphanol, a synthetic opioid, exerts analgesic and anti-inflammatory effects against pathogenic diseases. Butorphanol repressed malignant behaviors of tumor cells. In this study, the role of butorphanol in hepatocellular carcinoma was evaluated. Firstly, hepatocellular carcinoma cells were treated with butorphanol. The results showed that butorphanol decreased cell viability of hepatocellular carcinoma cells. Cell proliferation and metastasis of hepatocellular carcinoma cells were inhibited by butorphanol. Secondly, butorphanol suppressed angiogenesis, and reduced phosphorylation levels of p38 and JNK in hepatocellular carcinoma cells. Thirdly, butorphanol reduced in vivo tumor growth of hepatocellular carcinoma in nude mice. Butorphanol reduced tumor micro-vascular density (MVD) and repressed lung metastasis. In conclusion, butorphanol exerted anti-angiogenic and anti-metastatic effects on hepatocellular carcinoma and induced inactivation of MAPKs signaling.

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http://dx.doi.org/10.1038/s41429-022-00565-zDOI Listing

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