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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1492453
This article is part of the Research Topic Advancing Glioma Treatment: Novel Drugs, Mechanisms of Resistance, and Therapeutic Strategies View all articles

PACAP38 Synergizes with Irradiation to Suppress the Proliferation of Multiple Cancer Cells via Regulating SOX6/Wnt/β-catenin Signaling

Provisionally accepted
Ran Wu Ran Wu 1Chunxiang Cao Chunxiang Cao 1Lu Cao Lu Cao 1Jun Su Jun Su 2Keman Liao Keman Liao 1Huan Li Huan Li 1Qian Zhu Qian Zhu 1Shuyan Li Shuyan Li 1Min Li Min Li 1Jia-Yi Chen Jia-Yi Chen 1*
  • 1 Department of Radiation Oncology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
  • 2 Department of Oncology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

The final, formatted version of the article will be published soon.

    Background: Pituitary adenylate cyclase-activating polypeptide (PACAP) 38 is an endogenous neuropeptide with diverse functions, notably its critical role in inhibiting tumor proliferation. Radiotherapy is an important step in the standard treatment modality of many tumors. Combining radiotherapy with therapeutic agents represents a new and promising trend aimed at enhancing radiation sensitivity and improving tumor treatment efficacy. However, the efficacy of PACAP38 combined with radiotherapy on tumors has not yet been studied. Objective: This study aimed to investigate the impact of PACAP38, both independently and in combination with irradiation, on glioma and breast cancer cells, , while elucidating the underlying mechanisms involved. Method: We investigated the impact of PACAP38 independently and combined it with irradiation on glioma and breast cancer cells in vitro through cell counting kit-8, clonogenic formation, Edu assays, and in vivo through a xenograft tumor model. We further explored the molecular mechanisms underlying the inhibitory effects of PACAP38 on tumors using RNA sequencing, western blotting assay, immunohistochemistry, and immunofluorescence analysis. Further investigation of gene function and the downstream mechanism was carried out through small interfering RNA and overexpression lentivirus targeting the SRY-related high-mobility group box 6 (SOX6) gene and western blotting assay. Results: Our findings revealed that PACAP38 could effectively synergize with radiation to suppress the proliferation of glioma and breast cancer cells in vivo and in vitro. Molecular studies revealed that the inhibitory effect of PACAP38 on tumor cell proliferation was mediated by upregulating SOX6 protein expression through histone acetylation, thereby inhibiting the Wnt-β-catenin signaling pathway. Conclusion: PACAP38 synergizes with irradiation to suppress the proliferation of multiple cancer cells via regulating SOX6/Wnt/β-catenin signaling. This combination may represent a promising therapeutic strategy for cancer treatment, potentially improving outcomes for patients undergoing radiotherapy.

    Keywords: PACAP38, Cancer, Radiotherapy, Sox6, Wnt/β-catenin, histone

    Received: 06 Sep 2024; Accepted: 30 Sep 2024.

    Copyright: © 2024 Wu, Cao, Cao, Su, Liao, Li, Zhu, Li, Li and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Jia-Yi Chen, Department of Radiation Oncology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.