Inhibition of liver metastasis of colon cancer cells following treatment with Newcastle disease virus strain 7793: A preliminary observation in a mouse model
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Abstract:
Objective: To evaluate the liver metastasis-inhibiting and immune-stimulating effects of Newcastle disease virus (NDV) strain 7793 in a mouse model of colon cancer. Methods: CT26 colon cancer cells (1×106 cells in 0.1 ml PBS) were injected into the subcapsules of the spleen of BALB/c mice aged 4-6 weeks through intra-peritoneal injection. Surviving mice bearing CT26 colon cancer cells were randomized to receive PBS (0.1 ml/d), NDV7793 (512 HU/kg) and fluorouracil (5-FU, 20 mg/kg), respectively, for 5 days. Body weight and general health status were recorded before colon cancer cell transplantation, before the designated treatments and on post-treatment days 1, 5, 10 and 15, respectively. On post-treatment day 16, animals were sacrificed. Liver metastasis was assessed gross pathology. Thymus and liver were collected. Histologic assessment was performed on paraffin sections of the liver after H-E staining. Thymus index and metastasis inhibition rate were calculated. IFN-γ levels in the liver were measured by ELISA. Results: The metastatic foci in colon cancer cell-bearing mice were significantly less ( P <0.05) after treatment with NDV (20.40±5.20) and 5-FU (205.50±19.21) respectively than with PBS (265.30±35.73). Liver metastasis inhibition rate was significantly higher for NDV7793 than for 5-FU group (75.4% vs 48.0%, P <0.05). The mean survival time of colon cancer cell-bearing mice was 30 days after NDV7793 treatment, 22 days after 5-FU treatment but only 17 days after PBS treatment ( P< 0.05). Compared with PBS control group and 5-FU group, the increased Thymus index and liver concentrations of IFN-γ were significantly higher after treatment with NDV 7793 than with 5-FU and PBS respectively ( P <0.05). Conclusion: NDV 7793 appears effective to inhibit liver metastasis of colon cancer cells. This effect may be mediated by elevated IFN-γ in liver microenvironment.
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Project supported by the Foundation of the Ministry of Education for Doctoral Tutors(No. 20124503110007), the Natural Science Foundation of Guangxi Zhuang Autonomous Regin Province (No. 2014GXNSFAA118244),the Open Fund of Guangxi Medical Experiment Research Center(No. KFJJ2011-21), and the Graduate Innovation Fund of the Guangxi Zhuang Autonomous Regin Province (No. YCBZ2012014)