2. Academic Validation
  3. Dioscin potentiates the antitumor effect of suicide gene therapy in melanoma by gap junction intercellular communication-mediated antigen cross-presentation

Dioscin potentiates the antitumor effect of suicide gene therapy in melanoma by gap junction intercellular communication-mediated antigen cross-presentation

  • Biomed Pharmacother. 2022 Jun;150:112973. doi: 10.1016/j.biopha.2022.112973.
Wenbo Zhang 1,  Lingyun Lin 2,  Yujian Zhang 3,  Tingxiu Zhao 4,  Yujuan Zhan 5,  Huiqi Wang 6,  Junfeng Fang 7,  Biaoyan Du 8
Affiliations

Affiliations

  • 1 Department of Pathology and Pathophysiology, Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
  • 2 The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
  • 3 Panyu Hospital of Chinese Medicine, Guangzhou 511400, China.
  • 4 Department of Pathology and Pathophysiology, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
  • 5 Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
  • 6 Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
  • 7 First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China. Electronic address: gzyyfyfjf@163.com.
  • 8 Department of Pathology and Pathophysiology, Guangzhou University of Chinese Medicine, Guangzhou 510006, China. Electronic address: dubiaoyan@gzucm.edu.cn.
PMID: 35468581 DOI: 10.1016/j.biopha.2022.112973
Abstract

Dioscin (Dio), steroid saponin, exists in several medicinal herbs with potent Anticancer efficacy. This study aimed to explore the effect of Dio on the immune-related modulation and synergistic therapeutic effects of the herpes simplex virus thymidine kinase/ganciclovir (HSV-Tk/GCV) suicide gene therapy system in murine melanoma, thereby providing a research basis to improve the potential immunomodulatory mechanism underlying combination therapy. Using both in vitro and in vivo experiments, we confirmed the immunocidal effect of Dio-potentiated suicide gene therapy on melanoma. The results showed that Dio upregulated connexin 43 (Cx43) expression and improved gap junction intercellular communication (GJIC) in B16 cells while increasing the cross-presentation of antigens by dendritic cells (DCs), eventually promoting the activation and antitumor immune killing effects of CD8+ T lymphocytes. In contrast, inhibition or blockade of the GJIC function (overexpression of mutant Cx43 tumor cells/Gap26) partially reversed the potentiating effect. The significant synergistic effect of Dio on HSV-Tk/GCV suicide gene therapy was further investigated in a B16 xenograft mouse model. The increased number and activation ratio of CD8+ T lymphocytes and the levels of Gzms-B, IFN-γ, and TNF-α in mice reconfirmed the potential modulatory effects of Dio on the immune system. Taken together, Dio targets Cx43 to enhance GJIC function, improve the antigens cross-presentation of DCs, and activate the antitumor immune effect of CD8+ T lymphocytes, thereby providing insights into the potential immunomodulatory mechanism underlying combination therapy.

Keywords

Antigen cross-presentation; Dioscin; Gap junction intercellular communication; Immunoregulation; Melanoma; Suicide gene therapy.

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