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J Thorac Dis. 2019 Nov;11(11):4671-4681. doi: 10.21037/jtd.2019.10.58.

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.

Journal of thoracic disease

Yunhua Xu, Yan Pan, Zhen Zhou

Affiliations

  1. Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.
  2. Department of Pharmacy, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.

PMID: 31903256 PMCID: PMC6940230 DOI: 10.21037/jtd.2019.10.58

Abstract

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.

2019 Journal of Thoracic Disease. All rights reserved.

Keywords: Recombinant human thrombopoietin (rhTPO); carboplatin; gemcitabine (GEM); interleukin-2 (IL-2); lung carcinoma; mouse model

Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

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