CRABP2对肺癌细胞应答全反式视黄酸及细胞增殖的影响

Effect of CRABP2on lung cancer cells in response to all-trans retinoic acid and cell proliferation

目的探讨细胞视黄酸结合蛋白2(CRABP2)对肺癌细胞应答全反式视黄酸(ATRA)及细胞增殖的影响。方法观察两株肺癌细胞95-D和A549对ATRA的敏感性。应用小干扰RNA(siRNA)敲低CRABP2的表达,采用CCK-8和流式细胞术分别检测细胞增殖和周期变化,Western blot检测NF-κB和丝裂原活化蛋白激酶(MAPKs)信号通路分子的表达。结果 ATRA抑制95-D和A549细胞增殖,其中95-D细胞的抑制作用更为明显;而干扰CRABP2的表达则显著降低ATRA对95-D细胞的抑制作用。干扰CRABP2表达在一定程度上能直接抑制95-D细胞增殖,增加G1期的细胞比例,减少S期的细胞,降低NF-κB、应激活化蛋白激酶/c-JUN氨基末端激酶(SAPK/JNK)和c-JUN的磷酸化水平。结论 CRABP2能增强肺癌细胞对ATRA的敏感性,并且还可能通过调控NF-κB和SAPK/JNK信号通路促进细胞增殖,提示CRABP2在肿瘤细胞中的双重作用。

Objective To investigate the effect of cellular retinoic acid binding protein 2（CRABP2）on lung cancer cells in response to all-trans retinoic acid（ATRA）and cell proliferation.Methods The sensitivity of lung cancer cell lines 95-D and A549 to ATRA was observed.After CRABP2 expression was knocked down by siRNA in 95-D cells,the cell proliferation and cell cycle were detected by CCK-8and flow cytometry,respectively.The expressions of NF-κB and mitogenactivated protein kinases（MAPKs）were determined by Western blot.Results ATRA significantly inhibited the proliferation of both lung cancer cells,especially 95-D cells,which were then reversed by CRABP2 siRNA.Moreover,CRABP2 siRNA could directly inhibit the proliferation of 95-D cells,increase the cell proportion in G1 phase,decrease the cell proportion in S phase,and downregulate the phosphorylation levels of NF-κB,SAPK/JNK and c-JUN.Conclusion CRABP2 can enhance the sensitivity of lung cancer cells to ATRA,and may promote cell proliferation via regulating NF-κB and SAPK/JNK signaling pathway suggesting that CRABP2 plays dual roles in cancer cells.