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Updated: Aug 7, 2026
Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro
Published on: March 18, 2014
Interleukin-1 alpha increases the cytotoxic activity of etoposide against human osteosarcoma cells
Shu-Fang Jia1, Leonard A Zwelling, Amanda McWatters
1Department of Cancer Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Abstract:
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-1 alpha 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 microM etoposide was increased from 35 to 70%, 30 to 65%, and 4 to 90%, respectively, by 5.0 U/ml IL-1 alpha. 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-1 alpha treatment. IL-1 alpha 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.
Insights
Interleukin-1 alpha (IL-1 alpha) enhances etoposide chemotherapy effectiveness in osteosarcoma cells, offering a potential new treatment strategy for patients with recurrent pulmonary metastases.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Recurrent pulmonary metastases in osteosarcoma are a significant clinical challenge, often resistant to standard salvage chemotherapy.
- Etoposide shows limited efficacy in relapsed osteosarcoma patients, necessitating the exploration of novel therapeutic combinations.
Purpose of the Study:
- To identify novel combinations of biologic response modifiers and chemotherapeutic agents for osteosarcoma treatment.
- To investigate the potential of Interleukin-1 alpha (IL-1 alpha) in combination with chemotherapy to overcome drug resistance.
Main Methods:
- Osteosarcoma cell lines (MG-63, SAOS-2, TE-85) were treated with etoposide alone or in combination with IL-1 alpha.
- Cytostatic activity was assessed, and cytotoxicity was quantified using the colony-forming assay.
- Sensitivity to other chemotherapeutic agents (doxorubicin, cisplatin, topotecan) was also evaluated in the presence of IL-1 alpha.
Main Results:
- IL-1 alpha significantly increased the sensitivity of osteosarcoma cells to etoposide when administered simultaneously, enhancing cytostatic activity and reducing cell survival.
- The synergistic effect was observed only when IL-1 alpha preceded or was concurrent with etoposide, not when etoposide was given first.
- IL-1 alpha also enhanced sensitivity to doxorubicin but not to cisplatin or topotecan, suggesting a specific mechanism of action.
Conclusions:
- Simultaneous administration of IL-1 alpha and etoposide demonstrates a promising strategy to enhance chemotherapy efficacy in osteosarcoma.
- This combination therapy may overcome resistance mechanisms independent of p-glycoprotein, drug uptake, or topoisomerase II activity.
- Further clinical investigation of IL-1 alpha combined with etoposide is warranted for osteosarcoma patients with pulmonary metastases.
