Ovarian
mucinous adenocarcinoma (MAC) resists standard
chemotherapy and is associated with poor prognosis. A more effective treatment is needed urgently. The present study assessed the possibility of
molecular-targeted therapy with a novel dual inhibitor of
phosphatidylinositol 3'-kinase (PI3K) and
mammalian target of rapamycin (mTOR),
NVP-BEZ235 (
BEZ235) to treat of MAC. Seven human MAC cell lines were used in this study. The sensitivity of the cells to
BEZ235,
temsirolimus, and
anticancer agents was determined with the
WST-8 assay. Cell cycle distribution was assessed by flow cytometry, and the expression of
proteins in apoptotic pathways and molecules of the PI3K/Akt/mTOR signaling pathways was determined by Western blot analysis. We also examined the effects of
BEZ235 on
tumor growth in nude mice xenograft models. The cell lines showed half-maximal inhibitory concentration values of
BEZ235 from 13 to 328 nmol/L. Low half-maximal inhibitory concentration values to
BEZ235 were observed in MCAS and OMC-1 cells; these 2 lines have an activating mutation in the PIK3CA gene.
NVP-BEZ235 down-regulated the
protein expression of phosphorylated (p-) Akt, p-p70S6K, and p-4E-BP1, suppressed cell cycle progression, up-regulated the expression of cleaved PARP and cleaved
caspase 9, and increased apoptotic cells. Synergistic effects were observed on more than 5 cell lines when
BEZ235 was combined with
paclitaxel or
cisplatin. The treatment of mice bearing OMC-1 or RMUG-S with
BEZ235 significantly suppressed
tumor growth in MAC xenograft models without severe
weight loss. We conclude that the PI3K/Akt/mTOR pathway is a potential therapeutic target and that
BEZ235 should be explored as a therapeutic agent for MAC.