维甲酸和18β-甘草次酸联合抗人肺癌细胞增殖和侵袭作用的研究

Studies on proliferation inhibition and anti-invasion of retinoic acid and 18β-glycyrrhetinic acid in highly metastasized human lung cancer cell line

目的 探讨全反式维甲酸和 18β 甘草次酸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 维甲酸和甘草次酸处理PGCL3细胞 ,用细胞增殖抑制试验、软琼脂集落形成试验、对重建基底膜胶的侵袭试验、趋化运动试验和对层粘连蛋白的粘附试验以及组织蛋白酶B活性测定 ,观察细胞增殖和侵袭能力的变化。结果 维甲酸和甘草次酸可降低PGCL3细胞增殖能力 ,并呈剂量依赖性 ,IC50 分别为 12 .5 8μmol/L和 14 5 .3 μmol/L ;5 .0 μmol/L维甲酸、2 5 μmol/L和 5 0 μmol/L甘草次酸能抑制PG CL3细胞的侵袭能力 (P <0 .0 1和P <0 .0 0 1) ,且有剂量依赖性。 5 .0 μmol/L维甲酸和 2 5 μmol/L甘草次酸联合作用对细胞侵袭抑制率大于两药单独作用之和 ,呈协同作用。抗侵袭作用机理的分析结果显示上述各浓度的甘草次酸和 10 μmol/L维甲酸对细胞的运动、粘附、组织蛋白酶B分泌均有显著抑制作用 (P <0 .0 0 1) ,上述各浓度甘草次酸对软琼脂集落形成率有明显抑制作用 (P <0 .0 0 1)。结论 维甲酸和 18β 甘草次酸有抗PGCL3人肺癌细胞增殖和侵袭能力的作用 ,两药有协同抗侵袭作用 ,维甲酸和甘草次酸抗侵袭机理不是对侵袭过程中某一环节的阻断 ,而是对侵袭的各个基本环节都有抑制作用。

Objective To study the proliferation inhibition and anti invasion of retinoic acid (RA) and 18β glycyrrhetinic acid (GA) in highly metastasized lung cancer cell line (PGCL3), and to observe the combined effects of RA and GA. Methods The proliferation inhibitive rate, the colony formation rate in semi solid agar, the invasive ability to reconstituted basement membrane, the chemotatic migration ability, the laminin adhesion ability, and the activity of cathepsin B (CB) were tested. Results Treated with RA and GA, the proliferation of PGCL3 cells were inhibited obviously, and the inhibition degree was related to the dosage of the drugs. IC 50 of the proliferation inhibition were 12.58 μmol/L and 145.3 μmol/L respectively. Treated with 5.0 μmol/L RA, 25 μmol/L and 50 μmol/L GA, the invasive ability was decreased significantly (P<0.01 and P<0.001), and the inhibition was in a dose dependent manner. In combined treatment with 5.0 μmol/L RA and 25 μmol/L GA, the inhibition of invasion was greater than the sum of them used alone. Treated with GA of above concentrations and 10 μmol/L RA, the adhesion and migration ability and the secretion of CB of the PGCL3 cells were decreased significantly (P<0.001). Treated with GA of above concentation, the colony formation rate in semi solid agar was decreased significantly (P<0.001). Conclusion RA and GA can inhibit the proliferation and invasion of the PGCL3 human lung cancer cells and have the anti invasion synergism. The mechanism of anti invasion of RA and GA is to inhibit many points of invasive process.