2. Academic Validation
  3. Cepharanthine inhibits migration, invasion, and EMT of bladder cancer cells by activating the Rap1 signaling pathway in vitro

Cepharanthine inhibits migration, invasion, and EMT of bladder cancer cells by activating the Rap1 signaling pathway in vitro

  • Am J Transl Res. 2024 May 15;16(5):1602-1619. doi: 10.62347/WDFF7432.
Bo Chen 1 2,  Lin Chen 1 2,  Jin Yang 1 2,  Mingqiang Hou 3,  Qibo Cai 3,  Wenbin Dai 1 2,  Xin Zhou 1 2,  Weiwei Wang 1 2,  Xiaoming Long 4,  Na Yin 5
Affiliations

Affiliations

  • 1 Department of Urology, Zunyi Medical University Zunyi 563000, Guizhou, China.
  • 2 Department of Urology, Clinical Medical College and Affiliated Hospital of Chengdu University Chengdu 610000, Sichuan, China.
  • 3 Department of Urology, Xishui County People's Hospital Zunyi 563000, Guizhou, China.
  • 4 Department of Pharmacy, Clinical Medical College and Affiliated Hospital of Chengdu University Chengdu 610000, Sichuan, China.
  • 5 Department of Urology, The Third Affiliated Hospital of Zunyi Medical University Zunyi 563000, Guizhou, China.
PMID: 38883391 DOI: 10.62347/WDFF7432
Abstract

Background: Cepharanthine, a bioactive constituent of Stephania japonica (Thunb.) Miers, is known for its potent anti-tumor properties. Nevertheless, the precise impact of this substance on bladder Cancer remains poorly comprehended. The aim of this study was to demonstrate the effect and mechanism of cepharanthine on the metastasis of human bladder Cancer cells.

Methods: The application of network pharmacology was utilized to ascertain the possible targets and signaling pathways of cepharanthine in the treatment of bladder Cancer. The antiproliferative effects of cepharanthine were evaluated using Cell Counting Kit-8 and colony formation assays. The migration and invasion capabilities were assessed using Transwell assays and wound healing experiments. Proteins related to the Rap1 signaling pathway, cellular migration, cellular invasion, and Epithelial-Mesenchymal Transition (EMT) were quantified by western blotting.

Results: Through database screening, 313 cepharanthine-acting targets, 277 candidate disease targets in bladder Cancer, 22 intersecting targets, and 12 core targets were confirmed. The involvement of the Rap1 signaling system was revealed by the Kyoto Encyclopedia of Genes and Genomes' pathway enrichment study. Cepharanthine was shown to decrease bladder Cancer cell proliferation, migration, and invasion in vitro. Cepharanthine activated the Rap1 signaling pathway by upregulating Epac1 and downregulating E-cadherin and C3G protein expression, leading to increased expression of Rap1 GTP protein and decreased expression of protein kinase D1 and Integrin α5. Rap1 signalling pathway activation resulted in the downregulation of migration and invasion-related proteins, matrix metallopeptidase MMP2, MMP9, as well as EMT-related proteins, N-Cadherin and Snail, without affecting vimentin expression.

Conclusion: Cepharanthine inhibits migration, invasion, and EMT of bladder Cancer cells by activating the Rap1 signalling pathway. The results offer helpful insights regarding the possible therapeutic use of cepharanthine for treating bladder Cancer.

Keywords

Cepharanthine; Rap1 signaling pathway; bladder cancer; cell invasion; cell migration; network pharmacology.

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