视黄酸调节IL-1β和IFN-γ诱导肺癌细胞分泌C3及B因子的实验研究

Experimental study of effects of retinoic acid on IL-1β and IFN-γ induced C3 and factor B secretion in lung cancer cell line

背景与目的肺癌的发病率急剧上升,寻找有效的防治方法是迫切需要的。本研究旨在从免疫治疗的角度探讨近年来用于治疗恶性肿瘤的视黄酸(RA)与IL1β和IFNγ间的相互作用对人肺癌细胞株A549分泌C3及B因子(Bf)的影响。方法用ELISA、Westernblot的方法检测肺癌细胞株培养液中C3及Bf蛋白,用RTPCR法检测细胞核内C3及Bf的mRNA。结果ELISA、Westernblot和RTPCR法均显示IL1β和IFNγ促进A549细胞中C3和Bf的分泌及其mRNA的表达。视黄酸对A549细胞分泌C3及Bf没有影响,但它能进一步增强IL1β诱导的A549中C3、BfmRNA的表达和C3、Bf的分泌,以及IFNγ诱导的A549细胞中BfmRNA的表达和Bf的分泌。结论视黄酸可上调IL1β及IFNγ诱导人肺癌细胞株A549分泌C3及Bf,稳定补体系统激活因子与抑制因子间的平衡,对杀伤肿瘤细胞起到一定的作用,为临床上共同应用视黄酸与细胞因子治疗肺癌提供了理论依据。

Background and objective It is urgently necessary to research an effective method to prevent and treat lung cancer since its incidence has increased sharply. The aim of this study is to investigate the regulated effects of retinoic acid (RA) on IL-1β and IFN-γ induced C3 and factor B secretion in human lung cancer cell line A549. Methods C3 and factor B in cultured medium were measured in lung cancer cell line A549 by ELISA and Western blot, and their cellular mRNA levels were measured by RT-PCR analysis. Results ELISA, Western blot and RT-PCR results showed that IL-1β and IFN-γ could significantly increase C3 and factor B secretion and their mRNA levels in A549 cells. RA alone did not affect C3 and factor B level in A549 cells, but it could potentiated C3 and factor B secretion and their mRNA expression induced by IL-1β, as well as factor B secretion and its mRNA expression induced by IFN-γ. Conclusion RA can up-regulate C3 and factor B secretion induced by IL-1β and IFN-γ in human lung cancer cell A549. It may stabilize the balance between stimulator cytokines and inhibitor cytokines in complement system, and play a certain role in killing tumor cells. The results suggest that combination of RA and cytokines might be effective in the treatment of lung cancer.