伊班膦酸钠对小细胞肺癌溶骨性骨转移瘤细胞增殖抑制及凋亡影响的研究

目的观察伊班膦酸钠对体外培养的转移性小细胞肺癌细胞增殖抑制和凋亡的影响。方法选择术前未经任何治疗的6例溶骨性骨转移的肺癌患者,切取转移灶进行细胞培养;将处于对数生长期的骨转移瘤细胞分为2组,实验组加入不同浓度(2,4,8μg/L)的伊班膦酸钠,对照组加入同等质量分数的0.9%Na Cl,观察细胞形态学的差异及细胞对骨磨片的作用,并进行细胞增殖抑制实验及流式细胞术分析。结果实验组细胞数明显减少,形态变化明显,骨磨片上骨吸收陷窝形成减慢,数量减少;实验组随时间递增和浓度梯度递减,其细胞增殖抑制率逐渐增高;各浓度组处理小细胞肺癌细胞48 h后均使Bcl-2蛋白表达FI≤1.0(即阴性表达),随着作用剂量的增加,Bcl-2蛋白表达相对含量逐渐降低。结论在体外,实验条件下不同浓度的伊班膦酸钠均能够抑制转移性小细胞肺癌细胞增殖和诱导细胞凋亡,调控Bcl-2蛋白的表达,并呈现浓度和时间依赖性。

Study on biologic activity of ibandronate on osseous metastatic tumor cells of SCLC

Objective It is to observe the influence of ibandronate on the cell proliferation inhibition and apoptosis in osse- ous metastatic tumor cells of SCLC. Methods 6 cases of tumor tissues were obtained from osseous metastasis patient with lung cancer before any anti-tumor therapies were administrated. Logarithmic growth phase Cell of the experiment group were treated with ibandronate of different concentration （2, 4, 8 μg/mL） , and treated with 0.9% NaCl as a control. Cellular morphology and effect of cells on bone microspecimen were observed, and？ cell proliferation inhibition test and flow cytometry analysis were executed. Results Cells count of the experiment group was obviously decrease and with morphologic change. Absorption lacunas in the experimental group were lesser than control group. The formation of bone absorption lacuna was slow and the number was reduced. The cell proliferation inhibition effect was showed in a time and concentration dependent way. The ex- pression of Bcl -2 was down regulated in each concentration group after treated with ibandronate for 48 hours, and as the dose increased the expression of Bel - 2 relative reduction. Conclusion Ibandronate can inhibit the cell proliferation and induce ap- optosis by down-regulation of Bcl -2 expression in osseous metastasis SCLC in a dose and time independent way.