2. Academic Validation
  3. Therapeutic Potential of Regorafenib in Cisplatin-Resistant Bladder Cancer with High Epithelial-Mesenchymal Transition and Stemness Properties

Therapeutic Potential of Regorafenib in Cisplatin-Resistant Bladder Cancer with High Epithelial-Mesenchymal Transition and Stemness Properties

  • Int J Mol Sci. 2023 Dec 18;24(24):17610. doi: 10.3390/ijms242417610.
Feng-Che Kuan 1 2,  Jhy-Ming Li 3,  Yun-Ching Huang 4 5,  Shun-Fu Chang 6 7,  Chung-Sheng Shi 1 8
Affiliations

Affiliations

  • 1 Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
  • 2 Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital Chiayi Branch, Chiayi 61363, Taiwan.
  • 3 Department of Animal Science, National Chiayi University, Chiayi 60004, Taiwan.
  • 4 Division of Urology, Department of Surgery, Chang Gung Memorial Hospital Chiayi Branch, Chiayi 61363, Taiwan.
  • 5 Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
  • 6 Department of Medical Research and Development, Chang Gung Memorial Hospital Chiayi Branch, Chiayi 61363, Taiwan.
  • 7 Center for General Education, Chiayi Chang Gung University of Science and Technology, Chiayi 61363, Taiwan.
  • 8 Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital Chiayi Branch, Chiayi 61363, Taiwan.
PMID: 38139437 DOI: 10.3390/ijms242417610
Abstract

Bladder Cancer is becoming one of the most common malignancies across the world. Although treatment strategy has been continuously improved, which has led to cisplatin-based chemotherapy becoming the standard medication, Cancer recurrence and metastasis still occur in a high proportion of patients because of drug resistance. The high efficacy of regorafenib, a broad-spectrum kinase inhibitor, has been evidenced in treating a variety of advanced cancers. Hence, this study investigated whether regorafenib could also effectively antagonize the survival of cisplatin-resistant bladder Cancer and elucidate the underlying mechanism. Two types of cisplatin-resistant bladder Cancer cells, T24R1 and T24R2, were isolated from T24 cisplatin-sensitive bladder Cancer cells. These cells were characterized, and T24R1- and T24R2-xenografted tumor mice were created to examine the therapeutic efficacy of regorafenib. T24R1 and T24R2 cells exhibited higher expression levels of epithelial-mesenchymal transition (EMT) and stemness markers compared to the T24 cells, and regorafenib could simultaneously inhibit the viability and the expression of EMT/stemness markers of both T24R1 and T24R2 cells. Moreover, regorafenib could efficiently arrest the cell cycle, promote Apoptosis, and block the transmigration/migration capabilities of both types of cells. Finally, regorafenib could significantly antagonize the growth of T24R1- and T24R2-xenografted tumors in mice. These results demonstrated the therapeutic efficacy of regorafenib in cisplatin-resistant bladder cancers. This study, thus, provides more insights into the mechanism of action of regorafenib and demonstrates its great potential in the future treatment of cisplatin-resistant advanced bladder Cancer patients.

Keywords

bladder cancer; cisplatin resistance; epithelial–mesenchymal transition; regorafenib; stemness.

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