Suppression of nectin-2 induced early apoptosis in MDA-MB-468 triple-negative breast cancer cell line

Abstract

 Background: Breast cancer, the most common cancer in women, caused 670,000 deaths worldwide in 2022. Triplenegative breast cancer (TNBC), lacking estrogen (ER), progesterone (PR) and human epidermal growth factor (HER2) receptors, are especially aggressive with poor outcomes. Nectin-2 is overexpressed in breast cancer tissues and TNBC cell lines, suggesting a potential role in tumor progression and making it a candidate for further investigation.

Objective: To evaluate the role of nectin-2 in breast cancer progression, focusing on cell proliferation, apoptosis, and migration in the MDA-MB-468 TNBC cell line.

Methods:A stable NECTIN2-knockdown (KD) MDA-MB-468 cell line was generated using lentiviral transduction. Knockdown efficiency was confirmed by RT-qPCR and Western blot analysis. Cell proliferation was evaluated using the MTT assay, apoptosis was detected through Annexin-V/7-AAD staining, and migration was assessed via the transwell migration assay.

Results: Knockdown of NECTIN2 resulted in an 86% reduction at the gene level, with a corresponding protein reduction. The MTT assay showed that the knockdown of NECTIN2 has no significant effect on cell proliferation, and the transwell migration assay showed no notable difference in cell movement. However, there was a significant increase in early apoptotic cells to 17.26% in the NECTIN2 KD group.

Conclusion: Nectin-2 knockdown had no significant effect on proliferation and migration but slightly increased early apoptosis in MDA-MB-468 cells, suggesting a limited role in this model with moderate expression. Further studies across TNBC subtypes with varying nectin-2 levels are needed to clarify its role in tumor progression and potential as a therapeutic target.