IN-VITRO GROWTH EFFECTS OF COLONY-STIMULATING FACTORS IN OVARIAN-CANCER

Human recombinant colony-stimulating factors may be used to treat or p revent neutropenia caused by marrow toxic chemotherapeutic agents admi nistered to patients with cancer. Despite their common clinical use, l ittle is known about the potential adverse effects that these cytokine s may have on the growth of malignant cells. Indeed, several in vitro reports have indicated that colony-stimulating factors may act as stim ulating growth factors in some human malignancies. To evaluate these e ffects in ovarian cancer, we investigated the possible growth effects of granulocyte colony-stimulating factor (G-CSF/Filgrastim) and granul ocyte-macrophage colony-stimulating factors (GM-CSF/Sargramostim) on f our established ovarian cancer cell lines, as well as five primary ova rian cancer cultures over a wide range of pharmacologic doses. Cell vi ability was measured by an ATP bioluminescence assay and expressed as a percentage of untreated control cultures. G-CSF showed no growth-sti mulating effects in any of the four established cell lines tested . In the OVCAR-3 cell line, a decrease in growth (>10%) was seen at 10, 10 0, and 1000 ng/ml after 5 days of continuous treatment. In the same ce ll line, GM-CSF caused an increase (>10%) in growth at the same doses. However, these changes did not demonstrate statistical significance i n a dose-dependent fashion. In the five primary cultures treated with G-CSF, only one demonstrated statistically significant increases in gr owth in a dose-dependent manner. GM-CSF treatment had no significant g rowth alterations in these same five primary cultures. These results w ould suggest that colony-stimulating factors may act as growth factors in some but not all ovarian cancer cells. Further investigations into the receptor status of ovarian cancer cells for these cytokines are u nderway to clarify this issue. (C) 1994 Academic Press, Inc.