Effect of small molecule phosphatidylinositol 3-kinase inhibitor combined with 5-fluorouracil on regulating progression of breast cancer cells

Recent studies confirmed that phosphatidylinositol 3-kinase (PI3K) pathway is involved in regulating progression of breast cancer (BC), suggesting its potential as a novel therapeutic target. This study aimed to investigate the mechanisms by which the small molecule PI3K inhibitor BKM120, combined with 5-fluorouracil (5-FU), suppresses the malignant biological behaviors of human BC (HBC) cells. The HBC cells (MDA-MB-231) were randomized into four groups: Blank group (BG, regular culture), 5-FU group (10 μg/mL 5-FU treatment), BKM120 group (10 μmol/mL BKM120 treatment), and 5-FU + BKM120 group (combination treatment of 10 μg/mL 5-FU and 10 μmol/mL BKM120). Cell viability was assessed, while nuclear morphology was examined. The colony formation ability of cells was evaluated, and cell migration capacity was assessed. Flow cytometry was employed to analyze cell cycle (CC) changes, and western blotting determined expression levels of p-Akt, VEGF, and p53 protein. Relative to BG, both 5-FU and BKM120 groups demonstrated prominent reductions in cell viability, colony number, and wound healing rate. Additionally, nuclear fragmentation was observed, and G1 phase arrest occurred. The expression of p-Akt and VEGF proteins were greatly reduced, while p53 protein expression level was notably ( p < 0.05) increased in the treated cells. Neglectable differences were observed between 5-FU and BKM120 groups. In comparison to 5-FU and BKM120 groups, the 5-FU + BKM120 group exhibited a further drastic decrease in cell viability, colony number, and wound healing rate, with exacerbated nuclear fragmentation and more pronounced G1 phase arrest. Furthermore, p-Akt and VEGF protein levels were further reduced, while p53 protein expression level was substantially ( p < 0.05) increased. The small molecule PI3K inhibitor BKM120, in combination with 5-FU, notably suppresses proliferation, colony formation, and migration of HBC cells. This mechanism is likely associated with G1 phase arrest, reduced levels of Akt phosphorylation, decreased VEGF expression level, and increased p53 expression level.