甘草酸对人肺癌细胞增殖和侵袭抑制作用的机制探讨

Studies on the Mechanisms of Proliferative and Invasive Inhibition by Glycyrrhizin in Human Lung Cancer Cell

目的 探讨甘草酸对高转移人肺癌细胞 (PGCL3)增殖抑制、抗侵袭和诱导凋亡的作用 ,并探讨其抗增殖和侵袭作用的机制 .方法 用 0 .5mmol/L和 1.0mmol/L甘草酸处理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、粘附和运动试验 ,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 .上述两浓度处理细胞 4 8h ,用吖啶橙 -溴化乙锭荧光双染法和末端脱氧核苷酸转移酶标记法 (TUNEL法 )检测细胞凋亡 .结果 甘草酸使PGCL3细胞增殖抑制率升高 (p <0 .0 5和p <0 .0 1)和软琼脂集落形成率显著下降(p <0 .0 1) ,呈剂量依赖性 ,半增殖抑制浓度 (IC50 )为 1.8mmol/L ;甘草酸明显减弱细胞侵袭能力 (p <0 .0 1) ,涉及侵袭关键环节的细胞粘附、运动和组织蛋白酶B分泌均受明显抑制 (p <0 .0 5和p <0 .0 1) ;甘草酸还使细胞凋亡率显著升高 (p<0 .0 1) .结论 甘草酸具有抑制PGCL3人肺癌细胞增殖和侵袭作用 .其抑制增殖的机制是通过对细胞分化和凋亡的诱导作用 ;其抗侵袭机制是对侵袭的多个基本环节起抑制作用 .

Objective To study the effects of glycyrrhizin on proliferative inhibition, anti-invasion, apoptotic induction, and the mechanisms of proliferative and invasive inhibition in highly metastasis human lung cancer cells (PGCL3). Methods After PGCL3 cells were treated with 0.5mmol/L and 1.0mmol/L glycyrrhizin for 96 h, the inhibitive rate of proliferation, the colony-forming rate in semisolid agar, the invasion to reconstituted basement membrane, the laminin adhesion, the chemotactic migration and the activity of cathepsin B were tested to observe the effects of the glycyrrhizin on proliferation and invasion of PGCL3 cells. Treated with glycyrrhizin in the above concentration for 48 h, the rate of apoptosis were examined by the methods of acridine orange-ethidium bromide fluorescent stain and terminal deoxynucleotide transferase mediated dUTP nick-end-labelling. Results Treated with glycyrrhizin, the inhibitive rates of proliferation were increased (p<0.05 and p<0.01), and the colony-forming rates were decreased significantly (p<0.01). The degrees of their inhibitions were in a dose-dependent fashion. IC 50 of the proliferation inhibition was 1.8mmol/L. The invasive ability of PGCL3 cells was reduced significantly (p<0.01). The adhesive rate, migration ability and the secretion of cathepsin B of PGCL3 cells about the key points in the invasive process were inhibited obviously (p<0.05 and p<0.01). The rates of apoptosis of the cells were increased significantly (p<0.01). Conclusions Glycyrrhizin inhibits the proliferation and invasion of the PGCL3 cells. The mechanisms of proliferative inhibition of Glycyrrhizin are inducing effects on differentiation and apoptosis of the PGCL3 cells. The mechanisms of anti-invasion of Glycyrrhizin are to inhibit many key points in the invasive process.