TY - JOUR
T1 - Interferon-α enhances the sensitivity of human osteosarcoma cells to etoposide
AU - Jia, Shu Fang
AU - An, Taeha
AU - Worth, Laura
AU - Kleinerman, Eugenie S.
PY - 1999
Y1 - 1999
N2 - The purpose of these studies was to determine whether interferon-α (IFN-α) could enhance the sensitivity of human osteosarcoma cells to the cytotoxic actions of etoposide (VP-16). Cytostasis was determined using a [3H]thymidine incorporation assay, whereas cytotoxicity was quantified by a colony-formation assay. Low concentrations (0.1-5 U/ml) of IFN-α enhanced the cytostatic activity of VP-16 against MG-63, SAOS-2, and TE-85 osteosarcoma cells. The cytostatic activity of 1 μM VP-16 rose from 11% to 64%, 9% to 31%, and 10% to 71%, respectively, in the three cell lines when IFN-α was present. Survival fraction was also decreased when the osteosarcoma cells were treated with VP-16 + IFN-α as compared to either agent alone. The interaction between these two agents was determined to be synergistic rather than additive by interaction index analysis. Similar effects on cytostasis and cytotoxicity were observed when IFN-α was combined with Adriamycin but not cisplatin, actinomycin D, vinblastine, or amsacrine. VP-16 uptake was enhanced 12-fold in the presence of IFN-α, but this did not appear to translate into an increase in topoisomerase-II (topo-II)-DNA complex formation as quantified by the sodium dodecyl sulfate-KCl precipitation assay. We also could not detect alterations in topo-II expression, topo-II protein production, or cell cycle kinetics that have been shown to correlate with increased VP-16 cell sensitivity. Therefore, at this time the mechanism of enhanced cell sensitivity to the combination treatment remains unclear.
AB - The purpose of these studies was to determine whether interferon-α (IFN-α) could enhance the sensitivity of human osteosarcoma cells to the cytotoxic actions of etoposide (VP-16). Cytostasis was determined using a [3H]thymidine incorporation assay, whereas cytotoxicity was quantified by a colony-formation assay. Low concentrations (0.1-5 U/ml) of IFN-α enhanced the cytostatic activity of VP-16 against MG-63, SAOS-2, and TE-85 osteosarcoma cells. The cytostatic activity of 1 μM VP-16 rose from 11% to 64%, 9% to 31%, and 10% to 71%, respectively, in the three cell lines when IFN-α was present. Survival fraction was also decreased when the osteosarcoma cells were treated with VP-16 + IFN-α as compared to either agent alone. The interaction between these two agents was determined to be synergistic rather than additive by interaction index analysis. Similar effects on cytostasis and cytotoxicity were observed when IFN-α was combined with Adriamycin but not cisplatin, actinomycin D, vinblastine, or amsacrine. VP-16 uptake was enhanced 12-fold in the presence of IFN-α, but this did not appear to translate into an increase in topoisomerase-II (topo-II)-DNA complex formation as quantified by the sodium dodecyl sulfate-KCl precipitation assay. We also could not detect alterations in topo-II expression, topo-II protein production, or cell cycle kinetics that have been shown to correlate with increased VP-16 cell sensitivity. Therefore, at this time the mechanism of enhanced cell sensitivity to the combination treatment remains unclear.
UR - http://www.scopus.com/inward/record.url?scp=0032814630&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032814630&partnerID=8YFLogxK
U2 - 10.1089/107999099313758
DO - 10.1089/107999099313758
M3 - Article
C2 - 10433362
AN - SCOPUS:0032814630
SN - 1079-9907
VL - 19
SP - 617
EP - 624
JO - Journal of Interferon and Cytokine Research
JF - Journal of Interferon and Cytokine Research
IS - 6
ER -