Erythropoietin modulates the anticancer activity of chemotherapeutic drugs in a murine lung cancer model

In this study, we assessed the ability of erythropoietin (EPO) to synergize with various chemotherapeutic agents and suppress the growth and metastasis of solid tumors. Animals were inoculated with Lewis lung carcinoma (LLC) cells and treated with EPO alone, the designated chemotherapeutic drug (cisplatin, mitomycin C or cyclophoshamide) alone, or EPO and the drug. Tumor volume was monitored daily. Thirteen days following cell injection, tumor mass was determined. In addition, the number of the metastatic foci in the lungs was determined. Cisplatin alone was capable of inducing a 7-fold decrease in final tumor volume compared to tumor-bearing animals injected with saline. However, when EPO was combined with cisplatin, the animals experienced an 11-fold reduction in final tumor volume compared to saline-injected animals (P<0.001). A 2.5-fold reduction in tumor mass was observed in animals treated with cisplatin, compared to the saline-injected groups. Furthermore, injections of EPO and cisplatin induced a 4-fold reduction in tumor mass (P<0.001). Blood analysis indicated that a significant increase of more than 30% in WBC was found in animals injected concurrently with cisplatin and EPO, as compared to saline-injected mice (P<0.03). When EPO and mitomycin C were injected together, tumor mass was further reduced by 14% compared to that seen in mice treated with mitomycin C alone. However, this difference was not statistically significant. We conclude from this study that EPO can synergize with chemotherapeutic agents to further suppress the growth of tumors. The level of synergism is drug related.