流感病毒的抗肿瘤作用及其细胞凋亡机制的探索

Background: Based on the theory that viral multipolication could be done if host cells provide resource, energy and apparatus for viral biosynthesis and the reports which said that influenza virus could induce apoptosis on MDCK and Hela cells, we hypothesized that influenza virus can kill tumour cells by inducing apoptosis. The hypothesis was proved by vitro and vivo experiments..Methods: At first, we cultured influenza virus by embryonated chicken eggs. The virus was added to the plates in which tumour cells reached 75~90% confluence, including Hela, Raji, SMMC-7721 and SPC-A-1 strains. The apoptosis was observed by EM, DNA fragment analysis, and flow cytometry. sFasL in the supernatant was measured by ELISA. We also inoculated the virus into the mice in which S180 had been burdened. Then the survival rate and time were observed. Apoptosis effect in tumour cells was also checked. The samples were harvested and measured cytokines, including IL-2, IL-6 and TNF-α.Results: In the vitro experiments, the apoptosis occurred in the four experimental tumour cell lines after influenza virus infection. The concentration of sFasL in the supernatants of cultured Hela cells also increased. We also found the same result in Newcastle disease virus (NDV) to cultured tumour cells. In the vivo experiments, both average living time and survival rate of the experimental group mice were longer and higher than that of control group significantly. The cytokines' level also were higher than control, especially IL-2. Apoptosis cells were detected in experimented tumour cell..Conclusion: The results suggested that influenza virus can induce tumour cells to apoptosis and activated T cell mediated immunity. This study enriched the contents of oncolytic virus and oncolytic virual therapy for tumours. We also hope to find one new agent for bio-therapy of tumours through this research. .

培养和分离各型流感病毒，用它们分别注射于瘤荷瘤小鼠的实体瘤局部、及作用于体外培养的肿瘤细胞，观察其对肿瘤细胞的抑制和杀灭作用，检测肿瘤细胞的形态学改变、Fas抗原偷蛲鱿赴鸇NA条带出现情况，阐明其可能的抗肿瘤作用机制。本研究把病毒对宿主细胞的抑制和引起细胞凋亡的作用借鉴到抗肿瘤作用上，希望利用流感病毒为肿瘤的生长治疗探索一条新途径。