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IFN- Induces Apoptosis in Ovarian Cancer Cells in Vivo and in Vitro¹

Cancer Research UK, University Department of Oncology, Western General Hospital, Edinburgh EH4 2XU, United Kingdom [L. W., J. S.], and Cancer Research UK Translational Oncology Laboratory, Barts and The London, Queen Mary’s School of Medicine and Dentistry, London EC1M 6BQ, United Kingdom [F. Bu., C. B., F. Ba.]

Purpose: The purpose of this study was to compare in vitro and in vivo responses of primary human tumor cells to IFN-.

Experimental Design: IFN- may have therapeutic activity in patients with ovarian cancer. We showed previously that this cytokine had direct antiproliferative activity against human ovarian cancer cell lines and xenografts in nude mice. To further understand the role of IFN- in ovarian cancer, we compared its action on 8 ovarian cancer cell lines with the response of 14 primary cultures of ovarian tumor cells isolated from patients with ascitic disease. A pilot clinical study was then conducted to see whether IFN- would also induce apoptosis in human tumor cells in vivo. Six patients with ascites and advanced disease were given IFN- by i.p. injection, and sequential samples of ascites were analyzed.

Results: IFN- had antiproliferative activity in 8 of 8 ovarian cancer cell lines and 11 of 14 primary cultures. This activity was dose related, and cleaved poly(ADP-ribose) polymerase in protein isolates provided evidence of apoptosis. In the clinical study, there was a 3 log₁₀ pharmacokinetic advantage in peritoneal compared with plasma levels of IFN-. In two of six patients, there was a 90% reduction in tumor cells in ascites after IFN- treatment, and this was related to clinical benefit as assessed by intervals between paracentesis. In all six patients, there were increased amounts of cleaved poly(ADP-ribose) polymerase in protein extracts of ascitic cells sampled during IFN- treatment.

Conclusions: IFN- induces apoptosis in vitro and in vivo in human epithelial ovarian cancer.

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