维甲酸、甘草酸和18β-甘草次酸抗人肺癌细胞增殖和侵袭的作用

Effect of Retinoic Acid,Glycyrrhizin and 18β-Glycyrrhetinic Acid on Proliferation Inhibition and Anti-invasion in Human Lung Cancer Cells

[目的]探讨全反式维甲酸(RA)与甘草酸(GL)和18β鄄甘草次酸(GA)对高转移人肺癌细胞(PGCL3)增殖抑制和抗侵袭的作用及其联合作用。[方法]用2.5μmol/L和5.0μmol/LRA、0.5mmol/L和1.0mmol/LGL、25μmol/L和50μmol/LGA,以及5.0μmol/LRA与0.5mmol/LGL联合用药和5.0μmol/LRA与25μmol/LGA联合用药处理PGCL3细胞96h,进行细胞增殖抑制试验、软琼脂集落形成试验、侵袭、运动和粘附试验,以及组织蛋白酶B活性的测定,观察药物对PGCL3细胞增殖和侵袭能力的影响。[结果]RA、GL和GA可减弱PGCL3细胞增殖能力和侵袭能力(P<0.05和P<0.01),呈剂量依赖性,半增殖抑制浓度(IC50)分别为12.6μmol/L、1.8mmol/L和145.3μmol/L。RA与GL联合作用及RA与GA联合作用对细胞侵袭抑制率均大于两药单独作用之和,呈协同作用。GL和GA对细胞的运动、粘附、组织蛋白酶B分泌和软琼脂集落形成均有显著抑制作用(P<0.05和P<0.01)。[结论]RA、GL和GA均有抗PGCL3人肺癌细胞增殖和侵袭作用,RA与GL或GA联合作用均有协同抗侵袭作用,GL和GA抗侵袭机理是对侵袭过程中多个关键环节起抑制作用。

[Purpose]To explore the effects of retinoic acid(RA),glycyrrhizin(GL),18β-glycyrrhetinic acid(GA),the combination of RA and GL,and the combination of RA and GA on proliferation inhibition and anti-invasion in highly metastasis human lung can-cer cells(PGCL3).After PGCL3cells were treated with2.5μmol/L and5.0μmol/L RA,0.5mmol/L and1.0mmol/L GL,25μmol/L and50μmol/L GA,the combination of5.0μmol/L RA and0.5mmol/L GL,and the combination of5.0μmol/L RA and25μmol/L GA for96h.The effects on proliferation and invasion of PGCL3cells were examined by proliferation dependent manner fashion.inhibitive rate,colony-forming rate in semisolid agar,invasive ability,migration ability,adhesion ability,and activity of cathep-sin B(CB).Following treated with RA,GL and GA,the proliferation and invasive ability of PGCL3cells decreased signifi-cantly(P<0.05and P<0.01).The degrees of the proliferation inhibitions were in a dose-dependent manner fashion.IC 50 of the prolif-eration inhibitions were12.6μmol/L,1.8mmol/L and145.3μmol/L respectively.Following treated with the combination of RA and GL,and the combination of RA and GA,the inhibition of invasion was more significant than that treated with single drug alone.Fol-lowing.treated with GL and GA,adhesion and migration ability,secretion of CB and colony-forming rate in semisolid agar of the PG-CL3cells decreased significantly(P<0.05and P<0.01).[Conclusion]RA,GL and GA can inhibit the proliferation and invasion of the PGCL3cells.Their combination have synergistic effect.GL and GA may inhibit many key points in the invasive process.