Paclitaxel (PTX), one of the key drugs used to treat
ovarian cancer, activates the Raf-
mitogen-activated protein kinase kinase (
MEK) and
phosphatidylinositol 3'-kinase (PI3K) pathways, both considered to be proliferation and cell-survival pathways. The present study aimed to clarify whether and how
MEK and PI3K inhibitors affect sensitivity to PTX in
ovarian cancer cells. We treated five
ovarian cancer cell lines using PTX combined with
MEK inhibitor (
PD98059 [PD]) and PI3K inhibitor (
LY294002 [LY]), then assessed cell viability, apoptosis, and expression of phosphorylated (p)
MEK and pAkt. We also investigated the effect of combined treatment on survival in a xenograft model. The
protein expression levels of
MEK, pMEK, Akt, and pAkt were confirmed in all cell lines. pMEK levels increased after PTX treatment in all five
ovarian cancer cell lines. Combining PTX with either PD or LY had an additive effect on cell-growth inhibition. In contrast, we observed a synergistic effect when PTX was combined with both PD and LY. The number of apoptotic cells was significantly higher
after treatment with PTX combined with PD and LY, compared with PTX alone or PTX with either PD or LY (P < 0.05). PD with PTX downregulated the
protein expression level of pMEK and upregulated pAkt in all five cell lines. Treating nude mice with PTX and PD and LY prolonged survival in an
ovarian cancer xenograft model (P < 0.005). These results indicate that further study is warranted for PTX combined with
MEK inhibitor and PI3K inhibitor to treat ovarian
carcinoma.