Capecitabine regulates proliferation and apoptosis of ovarian cancer SKOV3 cells via the miR-29b-3p/MMP16 molecular axis

Objective: To investigate the molecular mechanism by which capecitabine regulates the proliferation and apoptosis of ovarian cancer SKOV3 cells through the miR-29b-3p/MMP16 axis.

Methods: SKOV3 ovarian cancer cells were treated with capecitabine, miR-29b-3p mimics, miR-29b-3p inhibitor, and MMP16 siRNA. Cell proliferation was measured using the CCK-8 assay, and apoptosis was assessed by flow cytometry. Changes in miR-29b-3p and MMP16 mRNA levels were analyzed via qRT-PCR, while protein expression of MMP16, Ki67, Caspase-3, and Bcl-2 were evaluated by Western blot. Target genes of miR-29b-3p were predicted using bioinformatics tools, and their interaction was validated through a luciferase reporter assay. Transfection of SKOV3 cells with a miR-29b-3p inhibitor or pcDNA-MMP16 was followed by capecitabine treatment, with subsequent analysis of cell proliferation and apoptosis.

Results: Capecitabine treatment reduced the viability of SKOV3 cells and promoted apoptosis, accompanied by increased miR-29b-3p expression and decreased MMP16 expression. Transfection with miR-29b-3p mimics or MMP16 siRNA also inhibited cell viability and enhanced apoptosis. Western blot analysis showed an increase in Ki67 and Caspase-3 expression and a decrease in Bcl-2 expression. Conversely, inhibition of miR-29b-3p or overexpression of pcDNA-MMP16 counteracted the effects of capecitabine, reversing the reduction in proliferation and the increase in apoptosis. Western blotting confirmed decreased Ki67 and Caspase-3 levels and increased Bcl-2 expression in these conditions.

Conclusion: Capecitabine enhances miR-29b-3p expression, leading to the downregulation of MMP16, thereby inhibiting proliferation and promoting apoptosis in ovarian cancer cells.