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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Ethnopharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1438161

Isoliensinine suppressed gastric cancer cell proliferation and migration by targeting TGFBR1 to regulate TGF-β-smad signaling pathways

Provisionally accepted
Jinda Hu Jinda Hu 1,2Shangming Dai Shangming Dai 1,2Mengqin Yuan Mengqin Yuan 1,2Fengjiao Li Fengjiao Li 1,2Shuoguo Xu Shuoguo Xu 1,2Lichen Gao Lichen Gao 1,2*
  • 1 Department of Pharmacy, School of Pharmacy, Phase I Clinical Trial Centre, The Afliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, China
  • 2 Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hengyang, China

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

    Background: Gastric cancer (GC) ranks as the fifth most prevalent cancer globally, and its pronounced invasiveness and propensity to spread provide significant challenges for therapy. At present, there are no efficacious medications available for the treatment of patients with GC. Isoliensinine (ISO), a bisbenzylisoquinoline alkaloid, was isolated from Nelumbo nucifera Gaertn. It possesses anti-tumor, antioxidant, and other physiological effects. Nevertheless, there is currently no available study on the impact of ISO on GC, and further investigation is needed to understand its molecular mechanism. Methods: ISO target points and GC-related genes were identified, and the cross-target points of ISO and GC were obtained. We then examined cross-targeting and found genes that were differentially expressed in GCs. Kaplan-Meier survival curves were used to screen target genes, and the STRING database and Cytoscape 3.9.1 were used to construct protein-protein interactions and drug-target networks. In addition, molecular docking studies confirmed the interactions between ISO screen targets. Finally, in vitro tests were used to establish the impact of ISO on GC cells. Results: Through bioinformatics research, we have identified TGFBR1 as the target of ISO in GC. In addition, we noticed a substantial inhibition in GC cell proliferation, migration, and invasion activities following ISO treatment. Moreover, we noticed that ISO treatment effectively suppressed TGF-β-induced epithelial-mesenchymal transition (EMT) and activation of the TGF-β-Smad pathway. Furthermore, we discovered that siTGFBR1 nullified the impact of ISO on TGF-β-triggered migration, invasion, and activation of the TGFβ-Smad pathway. Conclusion: Our research suggests that ISO specifically targets TGFBR1 and regulates the TGF-β-Smad signaling pathway to suppress the proliferation and migration of GC cells.

    Keywords: gastric cancer, Isoliensinine, Epithelial-mesenchymal transition(EMT), metastasis, proliferation, transforming growth factor-β(TGF-β)

    Received: 04 Jun 2024; Accepted: 10 Sep 2024.

    Copyright: © 2024 Hu, Dai, Yuan, Li, Xu and Gao. 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: Lichen Gao, Department of Pharmacy, School of Pharmacy, Phase I Clinical Trial Centre, The Afliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, 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.