Investigation of nedaplatin and CpG oligodeoxynucleotide combination therapy in a mouse model of lung cancer

Jianfeng Quan,Yanli Zhao

doi:10.4314/tjpr.v17i7.22

Abstract

Purpose: To investigate the anti-tumor effects of nedaplatin (NDP) and CpG oligodeoxynucleotide (CpG-ODN) combination therapy in a mouse-modeled lung cancer.Methods: To evaluate the anti-tumor effects of NDP and CpG-ODN combination therapy, a lung cancer xenograft mouse model was established by subcutaneous injection of LA-795 cells. BALB/c mice were divided into four groups as follows: NDP, CpG-, NDP + CpG-ODN and untreated control group. The sections of lung cancer tissue were stained with hematoxylin and eosin (H&E) and morphologically examined. Spleen, body weight, and spleen index were measured. Flow cytometry was used to determine the proportions of CD3+, CD8+, CD4+ and CD4+/CD8+ in mice blood cells. Serum levels of interferon-γ (IFN-γ) and interleukin-12 (IL-12) were measured by enzyme-linked immunosorbent assay (ELISA).Results: NDP + CpG-ODN therapy significantly reduced tumor volume and prolonged the survival time of tumor-bearing mice. NDP + CpG-ODN induced a change in cancer cell morphology, including large areas of necrosis which correlated with a reduction in tumor size. NDP + CpG-ODN significantly increased spleen weight/index and dramatically enhanced immune cell activation. This was evident in the increase serum levels of IFN-γ and IL-12.Conclusion: NDP and CpG-ODN combination therapy inhibits the growth of lung cancer and prolongs the survival time of tumor-bearing mice. This may result from the activation of immune cells and increased expression of IFN-γ and IL-12.Keywords: CpG ODN, NDP, Lung cancer, Combination therapy

Highlights

Lung cancer is a common malignant cancer with high morbidity and mortality rates
The sections were stained with hematoxylin and eosin (H&E) and images were captured by microscopy
From day 10 to day 22, there was a significant increase of tumor volume in the NDP + CpG oligodeoxynucleotide (CpG-ODN) combination group, compared to the CpG-ODN group and NDP group

Summary

INTRODUCTION

Lung cancer is a common malignant cancer with high morbidity and mortality rates. Lung cancer frequently results in organ metastasis, leading to death[1]. The effects of NDP + CpG-ODN combination therapy on lung cancer remains unknown. In order to better understand this relationship we established a lung cancer xenograft mouse model to evaluate the effects of NDP + CpG-ODN combination therapy, as well as, the mechanisms of NDP + CpG-ODN combination therapy. When the tumor volume reached 80 mm, sixty mice were randomly divided into 4 groups as follows: control group (no treatment), CpG-ODN group, NDP group, and NDP + CpG-ODN group. In the NDP group, the mice received 0.1 mL NDP (Aladdin Co., Shanghai, China) at a dose of 1 μg/mL. In the NDP + CpG-ODN combination therapy group, the mice received 0.1 mL CpGODN at a dose of 0.5 mg/mL and 0.1 mL NDP at a dose of 1 μg/mL. The sections were stained with hematoxylin and eosin (H&E) and images were captured by microscopy

Evaluation of spleen weight and index

RESULTS

DISCUSSION

CONCLUSION