TY - JOUR
T1 - Interleukin-1α increases the cytotoxic activity of etoposide against human osteosarcoma cells
AU - Jia, Shu Fang
AU - Zwelling, Leonard A.
AU - McWatters, Amanda
AU - An, Taeha
AU - Kleinerman, Eugene S.
PY - 2002
Y1 - 2002
N2 - The recurrence of pulmonary metastases resistant to salvage chemotherapy continues to be a major problem in osteosarcoma patients. Our goal is to identify novel combinations of biologic response modifiers plus chemotherapeutic agents that can be translated into clinical trials. Response rates of relapsed osteosarcoma patients to etoposide have been extremely low. The present investigation demonstrated that IL-1α dramatically increased the sensitivity of MG-63, SAOS-2, and TE-85 osteosarcoma cells to etoposide when the two agents were used simultaneously. The cytostatic activity of 1 μM etoposide was increased from 35 to 70%, 30 to 65%, and 4 to 90%, respectively, by 5.0 U/ml IL-1α. Analysis using the colony-forming assay to quantify cytotoxicity showed that the percentage of cell survival following exposure to etoposide decreased from 0.81 to 0.56, 0.55 to 0.2, and 0.4 to 0.05 when the combination treatment was used. Increased sensitivity was not seen when etoposide treatment preceded IL-1α treatment. IL-1α also increased the sensitivity of these cells to doxorubicin but not to cisplatin or topotecan. The mechanism of this enhanced activity is independent of p-glycoprotein, drug-uptake, or effects on topoisomerase II.
AB - The recurrence of pulmonary metastases resistant to salvage chemotherapy continues to be a major problem in osteosarcoma patients. Our goal is to identify novel combinations of biologic response modifiers plus chemotherapeutic agents that can be translated into clinical trials. Response rates of relapsed osteosarcoma patients to etoposide have been extremely low. The present investigation demonstrated that IL-1α dramatically increased the sensitivity of MG-63, SAOS-2, and TE-85 osteosarcoma cells to etoposide when the two agents were used simultaneously. The cytostatic activity of 1 μM etoposide was increased from 35 to 70%, 30 to 65%, and 4 to 90%, respectively, by 5.0 U/ml IL-1α. Analysis using the colony-forming assay to quantify cytotoxicity showed that the percentage of cell survival following exposure to etoposide decreased from 0.81 to 0.56, 0.55 to 0.2, and 0.4 to 0.05 when the combination treatment was used. Increased sensitivity was not seen when etoposide treatment preceded IL-1α treatment. IL-1α also increased the sensitivity of these cells to doxorubicin but not to cisplatin or topotecan. The mechanism of this enhanced activity is independent of p-glycoprotein, drug-uptake, or effects on topoisomerase II.
KW - Combination therapy
KW - Etoposide
KW - IL-1α
KW - Osteosarcoma
UR - http://www.scopus.com/inward/record.url?scp=0036007542&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036007542&partnerID=8YFLogxK
U2 - 10.1046/j.1359-4117.2002.01003.x
DO - 10.1046/j.1359-4117.2002.01003.x
M3 - Article
C2 - 12415617
AN - SCOPUS:0036007542
SN - 1359-4117
VL - 2
SP - 27
EP - 36
JO - Journal of Experimental Therapeutics and Oncology
JF - Journal of Experimental Therapeutics and Oncology
IS - 1
ER -