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ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Cancer Cell Biology
Volume 13 - 2025 |
doi: 10.3389/fcell.2025.1478648
Dioscin reverses Connexin-43 Channels deficiency induced EMT activation in gastric cancer via VEGFA/PI3K/Akt/mTOR pathway based on network pharmacology and experimental verification
Provisionally accepted- 1 Medical College, Yangzhou University, Yangzhou, China
- 2 Kunshan Qiandeng people's Hospital, Kunshan fifth People's Hospital, Suzhou, China., Kunshan, China
- 3 Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan Province, China
- 4 Luoyang Maternal and Child Health Hospital, Luoyang, Henan Province, China
Background: Dioscin, a natural compound extracted from Dioscorea nipponica Makino, has anticancer activities against specific types of cancer. However, the effect of dioscin against gastric cancer and its specific mechanism hasn't been determined.Methods: Wound healing, transwell assay and western blot were adopted to assess the effect of dioscin on gastric cancer (GC) in xenograft mice and cells. Network pharmacology and bioinformatics predicted the latent targets and related signaling pathway of dioscin and connexin 43 (Cx43) in gastric cancer. Protein overexpression and mutation were conducted to explore molecular mechanism. Results: Dioscin restrained malignancy and EMT of gastric cancer cells through Cx43-gap-junction-intercelluar-communications (Cx43-GJs). Network pharmacology and bioinformatics predicted potential targets and considered that Cx43 was relevant to VEGFA and PI3K-Akt pathway. Cx43 G21R mutation induced epithelial-mesenchymal transition (EMT)activation through activating the VEGFA/PI3K /Akt/ mTOR signaling pathway. Furthermore, activating Cx43-GJs as well as suppressing the VEGFA/PI3K/Akt/mTOR signaling pathway were dioscin mechanisms. Crucially, dioscin inhibited Cx43 G21R -induced malignancy of gastric cancer cells. Conclusion: Dioscin inhibited the tumor cell malignancy by activating Cx43-GJs as well as inhibiting VEGFA/PI3K/Akt/mTOR signaling pathway. Findings offer theoretical foundations for the latent application of dioscin to GC treatment via Cx43-GJs.
Keywords: gastric cancer, dioscin, Cx43-GJs, VEGFA, PI3K/Akt/mTOR signaling pathway, EMT
Received: 29 Oct 2024; Accepted: 17 Jan 2025.
Copyright: © 2025 Kou, Zhu, Shui, Tang, Gu, Wang and Han. 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:
Yu Kou, Medical College, Yangzhou University, Yangzhou, China
Rentao Zhu, Kunshan Qiandeng people's Hospital, Kunshan fifth People's Hospital, Suzhou, China., Kunshan, China
Menglin Shui, Medical College, Yangzhou University, Yangzhou, China
Huizi Tang, Medical College, Yangzhou University, Yangzhou, China
Feng Gu, Medical College, Yangzhou University, Yangzhou, China
Baowei Han, Luoyang Maternal and Child Health Hospital, Luoyang, Henan Province, China
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