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