Buspirone Hydrochloride: A Potential Regulator of PD-L1 for Enhanced Antitumor Activity in Melanoma-Bearing Mice

PD-1/PD-L1 blockade therapy shows good efficacy in melanoma treatment. Yet, most patients still exhibit poor responses. Exploring more effective drugs remains worthwhile. In contrast to developing new drugs which entails a lengthy process, high costs and uncertainties, repurposing old drugs is regarded as a promising and safe method, attracting greater attention. In this study, we evaluated the anti-melanoma effect of buspirone hydrochloride, a novel anti-anxiety drug. The results demonstrated that buspirone hydrochloride effectively restrained cell proliferation and migration and decreased the expression of related proteins p-STAT3, cyclin D1 and MMP2. Significantly, we discovered that buspirone hydrochloride efficiently enhanced the degradation of PD-L1. Further investigations in a melanoma-bearing mouse model showed that buspirone hydrochloride delayed the growth of tumors in tumor-bearing mice, increased apoptosis of tumor cells and inhibited cell proliferation. We found that buspirone hydrochloride treatment increased the ratio of T lymphocytes in the spleen of mice and the infiltration of T lymphocytes in tumor tissues. These findings suggest that buspirone hydrochloride not only plays an anti-melanoma role by directly inhibiting cell proliferation and promoting apoptosis but also enhances the anti-tumor immune response by suppressing PD-L1 expression, thus providing a new alternative for the development of melanoma treatment drugs.