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目的:研究白细胞介素23(IL-23)在小鼠乳腺癌中的抗肿瘤作用及其免疫功能变化。方法:将逆转录病毒介导转染IL-23基因的小鼠乳腺癌细胞(IL-23/MA-891)、转染逆转录病毒空载体的小鼠乳腺癌细胞(LXSN/MA-891)及亲代小鼠乳腺癌细胞(MA-891)分别接种于小鼠皮下,观察小鼠成瘤及肿瘤生长情况;30 d时取3组小鼠脾脏和肿瘤组织,用ELISA法检测3组小鼠脾细胞在MA-891诱导下IFN-γ、TNF-α、IL-12和IL-4的产生情况;用流式细胞术(FCM)检测肿瘤组织细胞表面分子MHC-Ⅰ、MHC-Ⅱ、CD80、CD86的表达,检测脾细胞中CD11c阳性细胞的比率,并对脾细胞中CD4+、CD8+淋巴细胞进行分选;用免疫组织化学技术对3组肿瘤组织中CD4+、CD8+淋巴细胞浸润情况进行检测。结果:IL-23基因转染组小鼠皮下结节生长速度明显慢于接种空载体转染组及未转染组;接种IL-23/MA-891细胞的小鼠脾细胞可产生较水平的IFN-γ、TNF-α和IL-12等Th1类及相关细胞因子,与接种LXSN/MA-891细胞和MA-891细胞2组小鼠的脾细胞相比明显增高(P<0.01),而Th2类细胞因子IL-4的水平却无统计学意义(P>0.05);接种IL-23/MA-891细胞组小鼠脾细胞中CD11c阳性细胞率、CD4+、CD8+淋巴细胞比率以及肿瘤组织中CD4+、CD8+淋巴细胞浸润程度均较LXSN/MA-891、MA-891组明显增加(P<0.01);IL-23/MA-891细胞组小鼠肿瘤组织细胞表面MHC-Ⅰ、MHC-Ⅱ、CD80、CD86分子的表达明显提高(P<0.01)。结论:转染IL-23基因的小鼠乳腺癌细胞所分泌的IL-23具有生物学活性,增强了细胞免疫功能,在小鼠体内发挥了明显的抗肿瘤作用。
Objective: To study the antitumor effect and immune function of interleukin-23 (IL-23) in mouse breast cancer. METHODS: Mouse breast cancer cells (IL-23 / MA-891) transfected with IL-23 gene and mouse breast cancer cells transfected with retroviral vector (LXSN / MA-891) And the parental mouse breast cancer cells (MA-891) were inoculated subcutaneously in mice respectively to observe the tumorigenesis and tumor growth of the mice. Three groups of mice spleen and tumor tissue were taken on the 30th day. Three groups of mice The production of IFN-γ, TNF-α, IL-12 and IL-4 in spleen cells induced by MA-891 was detected by flow cytometry (FCM). The expressions of MHC-Ⅰ, MHC- , CD86 expression were detected in spleen cells in the detection of CD11c-positive cells, and the spleen cells CD4 +, CD8 + lymphocytes were sorted by immunohistochemistry in three groups of tumor CD4 +, CD8 + lymphocyte infiltration were detected. Results: The growth of subcutaneous nodules in IL-23 gene transfection group was significantly slower than that in empty vector transfection group and non-transfection group; the spleen cells inoculated with IL-23 / MA-891 cells could produce more level Th1 and related cytokines such as IFN-γ, TNF-α and IL-12 were significantly higher (P <0.01) than splenocytes from two groups of mice inoculated with LXSN / MA-891 cells and MA-891 cells There were no significant differences in the levels of Th2 cytokines IL-4 (P> 0.05). The percentage of CD11c positive cells, CD4 +, CD8 + lymphocytes in splenocytes of IL-23 / MA- The infiltration rate of CD4 +, CD8 + lymphocytes in LXSN / MA-891 and MA-891 groups was significantly increased (P <0.01). The expressions of MHC-I and MHC- CD80, CD86 molecules significantly increased (P <0.01). CONCLUSION: IL-23 secreted by mouse breast cancer cells transfected with IL-23 gene has biological activity and enhances cellular immune function. It has obvious anti-tumor effect in mice.