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Turkish Journal of Biology

Abstract

Background/aim: HCC is a common and lethal malignancy and multi-kinase inhibitors (MKIs) are among the therapeutic options for unresectable cases. However, response rates to MKIs remained variable, necessitating the identification of predictive biomarkers. Plexin C1 (PLXNC1), a receptor involved in cell signaling, has emerged as a potential candidate to regulate tumor responses. This study aims to evaluate the impact of PLXNC1 expression on the sensitivity of HCC cells to MKI therapy.

Materials and methods: shRNA-mediated PLXNC1 knock-down and control clones of HCC cell lines PLC/PRF/5 and Hep3B were generated, and downregulation of PLXNC1 was confirmed using Western blotting. The effects of MKIs sorafenib and lenvatinib on apoptotic cell death and proliferation of HCC cell clones were explored in relation to PLXNC1 expression. Furthermore, tumor responses to MKIs were evaluated in mouse xenograft models engrafted with shPLXNC1 and control clones of PLC/PRF/5 cells.

Results: The results of our in vitro studies indicate that PLXNC1 expression is linked to heightened sensitivity of HCC cells to MKIs. Furthermore, the knockdown of PLXNC1 in these cells resulted in a reduction in proliferation and an increase in apoptosis resistance. The findings were validated in hepatocellular carcinoma (HCC) tumor models in immunodeficient mice, which revealed that cells expressing PLXNC1 were responsive to drug treatment. In PLXNC1-silenced cells, tumor volumes remained stationary, which was attributable to the antiproliferative effect of PLXNC1 knockdown.

Conclusion: PLXNC1 expression may serve as a predictive biomarker for MKI efficacy in HCC and provides a potential avenue for personalized therapeutic strategies. Further clinical validation is required to incorporate PLXNC1 into routine diagnostic and treatment protocols for HCC.

Author ORCID Identifier

GAMZE GÜNGÖR TOPCU: 0000-0002-0006-8844

ARZU AYSAN: 0000-0001-7217-3347

ŞEVVAL DİK: 0000-0002-6440-0201

MAİDE ŞEKER: 0000-0003-0013-2516

MELİKE BİNNUR BAHÇEKAPILI: 0009-0001-7950-2155

SUDE TOPKARAOĞLU: 0000-0002-7680-7156

DİLEK YAVUZER: 0000-0002-6024-7967

TAMER YAĞCI: 0000-0003-2050-7477

DOI

10.55730/1300-0152.2739

Keywords

Plexin C1, hepatocellular carcinoma, epithelial-to-mesenchymal transition, multikinase inhibitors

First Page

219

Last Page

232

Publisher

Scientific and Technological Research Council of Türkiye (TUBITAK)

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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