Open Access

ARTICLE

Plexin A2 Knockdown Enhances Apoptosis in Chemotherapy Treated Melanoma Cells

Nadezhda Palkina¹, Aleksandra Esimbekova¹, Ekaterina Lapkina¹, Victoriia Kutsenko¹, Ivan Zinchenko¹, Egor Dereviankin¹, Elena Anisimova², Andrei Savchenko², Tatiana Ruksha^1,*

1 Department of Pathophysiology, Krasnoyarsk State Medical University, Krasnoyarsk, Russia
2 Laboratory of Cell Molecular Physiology and Pathology, Federal Research Center, Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences, Krasnoyarsk, Russia

* Corresponding Author: Tatiana Ruksha. Email:

Oncology Research 2026, 34(5), 28 https://doi.org/10.32604/or.2026.069234

Received 18 June 2025; Accepted 29 January 2026; Issue published 22 April 2026

Abstract

Background: Cancer cells are characterized by the ability to exit reversibly from the cell cycle to resist an unfavorable environment. This study elucidates alterations in adhesion molecule expression in melanoma cells acquiring resistance to dacarbazine (DTIC) and entering the G0 state. Plexin A2 (PLXNA2) was identified as a focal adhesion-related molecule implicated in carcinogenesis. Methods: Applying siRNA-mediated knockdown, the effects of altered PLXNA2 expression in melanoma cells were evaluated. PLXNA2 expression was determined by real-time quantitative reverse transcription PCR, immunoblotting, and immunocytochemistry. Cell cycle phase distribution among dacarbazine-treated cells and their apoptosis levels were quantified by flow cytometry, while adhesion to fibronectin was evaluated spectrophotometrically. Results: Our findings indicated that DTIC treatment modulates melanoma cell interactions with the extracellular matrix, facilitating adhesion to collagen IV, fibronectin, and laminin. Concurrently, integrin expression diminishes upon DTIC exposure. Delete Crucially, focal adhesion signaling molecules, including PLXNA2, Phosphoinositide-3-Kinase Regulatory Subunit 1, and Fibroblast Growth Factor Receptor 2, exhibit increased expression. PLXNA2 knockdown in DTIC-treated melanoma cells did not affect the percentage of cells residing in the G0 phase of the cell cycle. However, it induced apoptosis in DTIC-treated SK-MEL-2 and A375 melanoma cells and G1 cell cycle arrest in A375 melanoma cells. Conclusions: These findings suggest that PLXNA2 down-regulation in DTIC-treated cancer cells promotes their apoptosis. Therefore, targeting focal adhesion molecules during chemotherapy can increase the sensitivity of tumor cells to anticancer treatment.

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