2. Academic Validation
  3. Buspirone hydrochloride: a potential regulator of PD-L1 for enhanced antitumor activity in melanoma-bearing mice

Buspirone hydrochloride: a potential regulator of PD-L1 for enhanced antitumor activity in melanoma-bearing mice

  • J Drug Target. 2026 Jan 12:1-14. doi: 10.1080/1061186X.2025.2611944.
Jiaxin Geng 1 2 3 4,  Kangle Wang 1 3 4,  Sheping Zhang 1 3 5,  Xiaofei Cheng 1 3 5,  Chifei Zhang 6 7,  Mingyu Mo 1 3 5,  Xingchan Ji 1 3,  Mingguang Shao 1 2 3,  Hanyu Jiang 1 3 5,  Mengyu Lei 1 3 5,  Sheng Guo 1 3 5,  Zishan Yang 1 3 5,  Yongxi Zhang 6 7,  Tian Wei 1 3 5,  Zhongwei Tian 8,  Yinghua Ji 2,  Tiesuo Zhao 1 3 5,  Huijie Jia 1 2 3
Affiliations

Affiliations

  • 1 Xinxiang Engineering Technology Research Center of Immune Checkpoint Drug for Liver-Intestinal Tumors, Xinxiang Medical University, Xinxiang, P.R. China.
  • 2 Department of Pathology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, P.R. China.
  • 3 Xinxiang Key Laboratory of Tumor Vaccine and Immunotherapy, Xinxiang Medical University, Xinxiang, P.R. China.
  • 4 Department of Medical Oncology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
  • 5 Department of Immunology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, P.R. China.
  • 6 Department of Oncology, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, P.R. China.
  • 7 Xinxiang Key Laboratory for Tumor Radiotherapy and Targeted Therapy, Xinxiang, P.R. China.
  • 8 Department of Dermatology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
PMID: 41489440 DOI: 10.1080/1061186X.2025.2611944
Abstract

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 tumours in tumour-bearing mice, increased Apoptosis of tumour 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 tumour 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-tumour immune response by suppressing PD-L1 expression, thus providing a new alternative for the development of melanoma treatment drugs.

Keywords

Buspirone hydrochloride; PD-L1; drug repurposing; immunotherapy; melanoma.

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