RNA interference-mediated silencing of the phosphatidylinositol 3-kinase catalytic subunit attenuates growth of human ovarian cancer cells in vitroand in vivo.

OBJECTIVE: The phosphatidylinositol 3-kinase (PI3K) pathway plays a critical role in ovarian cancer cell survival and proliferation. The aim of this study was to determine whether the suppression of the PI3K catalytic subunit p110alphainhibits the growth of ovarian cancer cells in vitro and in vivo.

METHODS: The short hairpin RNA (shRNA) was used to knock down the expression of p110alpha in SKOV3 human ovarian cancer cells. The effects of shRNA on cell viability and apoptosis in vitro were assessed using the MTT assay and flow-cytometric analysis. Furthermore, the growth inhibition capacity of shRNA on ovarian carcinoma xenografts was tested in nude mice. Tumor cell proliferation, apoptosis and angiogenesis were measured by proliferating cell nuclear antigen, TUNEL and CD31 immunohistochemistry, respectively.

RESULTS: Using sequence-specific shRNA, we have silenced the expression of p110alpha in SKOV3 cells. shRNA-mediated knockdown of p110alpha correlated in vitro with decreased cell viability and increased apoptosis. Furthermore, inhibition of p110alpha significantly delayed the growth of ovarian carcinoma xenografts, and ultimately resulted in decreased cell proliferation, induction of apoptosis as well as a reduction in microvessel density.

CONCLUSIONS: Our findings suggest that shRNA-directed targeting of p110alpharaises the potential of its application in human ovarian cancer therapy.