Effect of silibinin on GAS6/sAXL and JAK/STAT pathways in human cholangiocarcinoma cell line


Caliskan Z. N., ÖZEL YETKİN M., BAŞKOL M., BAŞKOL G.

Turkish Journal of Biochemistry, vol.49, no.5, pp.637-646, 2024 (SCI-Expanded) identifier

  • Publication Type: Article / Article
  • Volume: 49 Issue: 5
  • Publication Date: 2024
  • Doi Number: 10.1515/tjb-2022-0275
  • Journal Name: Turkish Journal of Biochemistry
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Food Science & Technology Abstracts, Directory of Open Access Journals
  • Page Numbers: pp.637-646
  • Keywords: apoptosis, cholangiocarcinoma, GAS6/AXL signaling pathway, JAK/STAT signaling pathway, silibinin
  • Erciyes University Affiliated: Yes

Abstract

Cholangiocarcinoma (CCA) is a highly heterogeneous biliary malignant tumor. Studies have demonstrated that JAK/STAT signaling is activated in many types of cancer. In addition, JAK/STAT is activated downstream of AXL, and the AXL receptor is activated by its ligand, GAS6. In this study, we investigated the anticarcinogenic effect of silibinin and its relationship with the GAS6/AXL ve JAK/STAT pathway in the human EGI-1 cell line. Cell viability, apoptosis, and cell cycle were measured by Muse Cell Analyzer. All the protein levels were determined by the ELISA method. We observed that silibinin significantly reduced cell proliferation and colony formation (p<0.05, p<0.001, respectively). Silibinin also significantly induced total apoptosis and the G0/G1 phase of the cell cycle (p<0.01). We observed that silibinin significantly decreased JAK2 levels while increased STAT1 levels compared to the controls respectively (p<0.001; p<0.001). Besides, silibinin statistically decreased the levels of sAXL; however, numerically, but not statistically, it increased the level of GAS6 (p>0.05). Silibinin reduces colony formation, inducing apoptosis and arresting cancer cells in the G0/G1 phase, which is an indicator of its anticancer activity. In addition, silibinin decreased the levels of JAK2 and sAXL, which contributes to the development of cancer, and increased the levels of STAT1, suggesting silibinin's antiproliferative effects.