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目的:研究黑色素瘤分化相关基因-7(melanoma differentiation associated gene 7,MDA-7)/IL-24对Burkitt淋巴瘤细胞的促分化作用并探讨其作用机制。方法:构建稳定过表达MDA-7/IL-24的人Burkitt淋巴瘤Raji和Daudi细胞株,MTS法检测稳定转染MDA-7/IL-24对Raji和Daudi细胞活力的影响;Transwell小室实验检测转染MDA-7/IL-24对Raji和Daudi细胞侵袭和迁移能力的影响;流式细胞术检测细胞凋亡水平及免疫表型;Western blotting技术检测转染MDA-7/IL-24对Raji和Daudi细胞表达分化相关蛋白Myb、BLIMP1及BCL-6的影响;建立裸鼠Raji细胞移植瘤模型,检测在体内环境中稳定转染MDA-7/IL-24对Raji细胞生物活性的影响。结果:过表达MDA-7/IL-24的Raji和Daudi细胞其增殖(P<0.05)、侵袭(P<0.01)及迁移(P<0.01)能力均明显下降,但凋亡细胞无明显增加(P>0.05),表达CD45及CD138的水平均明显增加(P<0.01),而表达CD10的水平明显下降(P<0.01)。过表达MDA-7/IL-24的Raji和Daudi细胞表达BLIMP1的水平明显增加(P<0.01),而表达Myb及BCL-6的水平均明显减低(P<0.01)。MDA-7/IL-24过表达组裸鼠模型Raji细胞移植瘤质量明显低于对照组[(1.23±0.21)vs(1.96±0.24)g,P<0.01]。结论:转染MDA-7/IL-24可能通过诱导分化作用抑制Burkitt淋巴瘤细胞的生物活性。
Objective: To investigate the effect of melanoma differentiation associated gene 7 (-7-melanoma differentiation associated gene 7) on the differentiation of Burkitt lymphoma cells and to explore its mechanism. Methods: Raji and Daudi cell lines stably expressing human Burkitt’s lymphoma over-expressing MDA-7 / IL-24 were constructed. The effects of stably transfected MDA-7 / IL-24 on the cell viability of Raji and Daudi cells were detected by MTS. Transwell chamber assay The effects of MDA-7 / IL-24 on the invasion and migration of Raji and Daudi cells were detected by flow cytometry. The apoptosis and immunophenotype were detected by flow cytometry. To investigate the effect of MDA-7 / IL-24 on the proliferation of Raji cells in nude mice. To investigate the effect of MDA-7 / IL-24 on Raji cells in vivo. Results: Raji and Daudi cells overexpressing MDA-7 / IL-24 had significantly decreased proliferation (P <0.01), migration (P <0.01), but no significant increase in apoptotic cells P> 0.05). The levels of CD45 and CD138 were significantly increased (P <0.01), while the level of CD10 expression was significantly decreased (P <0.01). The level of BLIMP1 was significantly increased in Raji and Daudi cells overexpressing MDA-7 / IL-24 (P <0.01), while the levels of Myb and BCL-6 were significantly decreased (P <0.01). The tumor mass of Raji cells in MDA-7 / IL-24 overexpression group was significantly lower than that in control group [(1.23 ± 0.21) vs (1.96 ± 0.24) g, P <0.01]. CONCLUSION: Transfection of MDA-7 / IL-24 may inhibit the biological activity of Burkitt’s lymphoma cells by inducing differentiation.