Human recombinant
colony-stimulating factors may be used to treat or prevent
neutropenia caused by marrow toxic chemotherapeutic agents administered to patients with
cancer. Despite their common clinical use, little is known about the potential adverse effects that these
cytokines may have on the growth of malignant cells. Indeed, several in vitro reports have indicated that
colony-stimulating factors may act as stimulating
growth factors in some human
malignancies. To evaluate these effects in
ovarian cancer, we investigated the possible growth effects of
granulocyte colony-stimulating factor (
G-CSF/
Filgrastim) and granulocyte-macrophage
colony-stimulating factors (
GM-CSF/
Sargramostim) on four established
ovarian cancer cell lines, as well as five primary
ovarian cancer cultures over a wide range of pharmacologic doses. Cell viability was measured by an
ATP bioluminescence assay and expressed as a percentage of untreated control cultures.
G-CSF showed no growth-stimulating 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, 100, and 1000 ng/ml after 5 days of continuous treatment. In the same cell line,
GM-CSF caused an increase (> 10%) in growth at the same doses. However, these changes did not demonstrate statistical significance in a dose-dependent fashion. In the five primary cultures treated with
G-CSF, only one demonstrated statistically significant increases in growth in a dose-dependent manner.
GM-CSF treatment had no significant growth alterations in these same five primary cultures. These results would 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 underway to clarify this issue.