Ad-PUMA sensitizes ovarian cancer cells to chemotherapeutic agents.

OBJECTIVE: Ovarian cancer accounted for the first cause of death in female reproductive system tumor even with the operation and chemotherapy. We sought to evaluate the therapeutic potential of p53 up-regulated modulator of apoptosis (PUMA) in ovarian cancer.

MATERIALS AND METHODS: An adenovirus expressing PUMA (Ad-PUMA), alone or in combination with chemotherapeutic agents, was used to treat two different ovarian cancer cell lines. The mechanism of PUMA-mediated growth suppression and apoptosis was investigated by analysis of caspase-9 activation and the change of mitochondrial membrane potential (Δψm).

RESULTS: The exogenous PUMA was expressed 6 h after Ad-PUMA infection, which increased the chemosensitivity of the cancer cells and decreased the IC50 of chemotherapeutic agents compared with uninfected cells. The apoptotic percentage of OVCAR-3 and SKOV3 increased greatly compared with Taxol or Cisplatin alone. There was shear zone in caspase-9 and Δψm decrease after Ad-PUMA infection which suggested apoptosis started in mitochondrial mediated pathway.

CONCLUSIONS: PUMA plays a role in suppressing tumor growth and sensitizing ovarian cancer cells to anticancer drugs and may be a promising tool for cancer biotherapy.