Recombinant human thrombopoietin combined with interleukin-2 improves the effects of chemosensitivity and thrombocytopenia on a basic gemcitabine and carboplatin combination therapy for non-small cell lung cancer in a nude mouse model

摘要

Background: To investigate the effects of recombinant human thrombopoietin (rhTPO) and interleukin-2 (IL-2) on a basic gemcitabine (GEM) plus carboplatin (GC) treatment regimen in a murine lung carcinoma model. Methods: Fifty nude mice with subcutaneous tumors derived from human lung cancer cells were divided into 5 groups, each comprised of 10 mice: A blank group (intraperitoneal injection of saline), a control group (GC) (intraperitoneal injections of GC), a rhTPO group (same as the control group plus subcutaneous injection of rhTPO), an IL-2 group (same as the control group plus subcutaneous injection of IL-2) and a rhTPO + IL-2 group (same as the rhTPO group plus subcutaneous injection of IL-2). Tumor development and histology as well as CD4+, phosphorylated-adenosine monophosphate-activated protein kinase (p-AMPK), phosphorylated-protein kinase B (p-AKT), phosphorylated-extracellular signal-regulated kinase (p-ERK), phosphorylated-phosphoinositide 3-kinase (p-pI3K) and GTPase RAS1 expression in tumor tissues were measured and blood analyses performed. Results: Tumor sizes from all treated mice were significant smaller than the controls, as were the tumors of IL-2 plus GC treated mice compared to other treated groups. CD4+ expressing cells were increased in tumors after IL-2 and rhTPO treatment and the application of rhTPO significantly restored the blood platelet count. The expression of p-AMPK, p-AKT, p-ERK, p-pI3K and RAS1 in tumor cells were all significantly diminished after the addition of rhTPO and IL-2 to the GC regimen. Conclusions: The supplementation of rhTPO and IL-2 to a GC regime effectively reduced tumor sizes and restored the platelet count in a human lung cancer mouse model.