洛罗兰糖苷激活Bcl-2通路诱导髓样抑制性细胞凋亡研究

Study on loroglossin induced myeloid derived suppressor cells apoptosis via activating the Bcl-2 signaling pathway

关键词:  洛罗兰糖苷  抑制肿瘤生长  髓样抑制性细胞  细胞凋亡

Key words:  loroglossin  anti-tumor  myeloid derived suppressor cells  apoptosis

摘要:

[目的]促进髓样抑制性细胞（MDSCs）凋亡是抑制肿瘤生长的一个有效途径。因此，该实验旨在探究盘龙参活性成分络罗兰糖苷对MDSCs的抑制效应以及可能机制。[方法]采用MTT法分别检测洛罗兰糖苷对MDSCs细胞系（MSC-2）的毒性；采用流式分析法检测洛罗兰糖苷对MSC-2的促凋亡作用；采用聚丙烯酰胺凝胶电泳检测洛罗兰糖苷作用后MSC-2细胞内凋亡相关基因的蛋白表达水平。[结果]细胞活性检测证实洛罗兰糖苷可以抑制MSC-2的活性；凋亡抗体染色结果显示洛罗兰糖苷可以促进MSC-2凋亡；Western Blot结果表明，洛罗兰糖苷作用下，JNK2、细胞色素C、caspase-9、caspase-3表达明显上调，而Bcl-2表达下降。[结论]洛罗兰糖苷可以通过激活Bcl-2信号通路，促进MDSCs凋亡增强免疫正调控，从而达到抗肿瘤的效果。

Abstract:

[Objective] Promoting the apoptosis of myeloid derived suppressor cells is an effective way to inhibit tumor growth. Therefore,this experiment aimed to explore the inhibitory effect and mechanism of loroglossin extracted from Spiranthes sinensis (Pers.) Ames[Neottia sinensis Pers.] on MDSCs.[Methods] MTT assay was used to detect the toxicity of loroglossin to MDSC cell lines. Pro-apoptotic effect of loroglossin on MSC-2 was determined by flow analysis. Western blot was used to detect the protein expression levels of apoptosis-related proteins in MSC-2 cells.[Results] Loroglossin treatment resulted in a dose-dependent decrease in cell proliferation and induced apoptosis in MDSCs. Subsequent analysis showed that loroglossin treatment enhanced activation of JNK2,cytochrome C,caspase-9 and caspase-3,and downregulated the expression levels of Bcl-2.[Conclusion] Loroglossin could promote the apoptosis of MDSCs and enhance the positive immune regulation through activating the Bcl-2 signaling pathway. Loroglossin is promising as a new drug for clinical treatment of cancer.