Effects Of PI3K Inhibitor On The Proliferation And Migration Of Triple-negative Breast Cancer Cell Lines

Objective: To study the effects of PF-04691502, a phosphoinositide3-kinase(PI3K) inhibitor, on the proliferation, colony formation, migrationand cell cycle of triple-negative breast cancer(TNBC) cell lines.Due to the clinical therapy of TNBC was difficult, so the effects ofPF-04691502in combination with carboplatin, a chemotherapy drug, orgefitinib, a epidermal growth factor receptor(EGFR) inhibitor, on TNBCcell lines(HCC1937and MDA-MB231) were researched.Methods:(1) Effects of PF-04691502on the ability of proliferation,colony formation and migration of TNBC cell lines were measured by theMTS, colony formation, wound-healing. And the preliminary study onmechanism had been researched by flow cytometry and ELISA.(2) Effects of PF-04691502in combination with carboplatin andgefitinib, respectively, on proliferation were evaluated by combinationindex. And the combined effects were also studied by clone formation,wound-healing, ELISA, etc. Results:(1) PF-04691502prevented the proliferation of HCC1937andMDA-MB231cell lines, and the value of IC50were0.1μmol/L and0.4μmol/L respectively. It also prevented colony formation and migration ofTNBC cell lines, inhibited the Akt phosphorylation of these cell lines, andretarded the cells in G1phase(P<0.05).(2) Significant synergistic effects were observed in proliferation assay,colony formation assay, migration assay and Akt phosphorylation assaywhen small dose of PF-04691502in combination with carboplatin orgefitinib. PF-04691502in combination with gefitinib retarded the cells inG1phase, and the comparison between the combination group andmonotherapy group, the difference has statistical significance(P<0.05).Conclusions:(1) PI3K inhibitor could prevent the proliferation, colonyformation and migration of TNBC cell lines(HCC1937and MDA-MB231),mechanisms of which may relate with it’s inhibition of Akt phosphorylationand G1phase arrest.(2) PF-04691502in combination with carboplatin or gefitinib hadsignificant synergistic effects. And combination could improve the activityto cancer cell lines, decrease the dosage, and reduce the side effects.(3) PI3K inhibitor could improve the inhibitory effect of carboplatinand gefitinib on TNBC cell lines.