双膦酸盐对肺癌细胞增殖的影响

Effects of bisphosphonates on proliferation of lung cancer cells in vitro

背景与目的双膦酸盐在临床上被广泛用于多种骨病的治疗,在动物实验中可减少乳腺癌及前列腺癌细胞骨转移的发生,抑制和减少肿瘤在骨上的发展及负累,但对同样易于发生骨转移的肺癌的作用尚缺少研究。本实验的目的是研究几种双膦酸盐(阿仑膦酸钠、埃本膦酸钠、亚甲基二膦酸钠及因卡膦酸二钠)对不同肺癌细胞体外增殖的抑制作用,并验证这种抑制作用的广泛性或者选择性。方法采用磺酰罗丹明B染色法检测不同浓度的双膦酸盐药物对肺癌细胞及人正常肝细胞体外增殖的影响。结果不同浓度的双膦酸盐药物作用72h后,能不同程度地抑制肺癌细胞的增殖,亚甲基二膦酸钠的抑制效果很小,埃本膦酸钠及因卡膦酸二钠的作用介于亚甲基二膦酸钠和阿仑膦酸钠之间。不同的双膦酸盐对人正常肝细胞的影响具有差异性,亚甲基二膦酸钠、埃本膦酸钠及因卡膦酸二钠均表现出低毒性,而阿仑膦酸钠的毒性显著。不同的肺癌细胞对双膦酸盐的敏感性也有明显差异,H446及SPCA1相对较为耐受,而H460及A549则较为敏感。结论双膦酸盐药物对肺癌细胞及人正常肝细胞均有不同程度的抑制增殖作用,且这种作用与药物种类、浓度和肺癌细胞的种类有关。

Background and objective Bisphosphonates have been used to treat many bone diseases in clinic. Bisphost）honates have also been proven useful in the management of bone metastasis in patients with breast and prostate carcinoma as demonstrated in a number of trials in vitro and in vivo, but, it is little known that the effect of bisphosphonates on lung cancer, one of the most common hone metastatic malignant tumors. This study is to investigate the effect of several bisphosphonates on inhibiting proliferation of different lung cancer cell lines in vitro, and to validate whether this inhibitive effect is comprehensive or selective. Methods The cytotoxic effect of bisphosphonates on lung cancer cells and human normal liver cells was determined by sulforhodamine B （SRB） assay. Results After incubation of lung cancer cells with bisphosphonates for 72 h, the proliferation was inhibited in different degrees. The inhibiting activity of medronate （MDP） was the lowest, while the activity of ibandronate and incadronate （YM175） was between MDP and alendronate. The effects of bisphosphonates on human normal liver cells were different. The toxicity of MDP, ibandronate and YM175 was low, while alendronate had high toxicity. The sensitivity of lung cancer cells to bisphosphonates was also different. The sensitivity of H446 and SPC-A1 was comparatively lower, while H460 and A549 were more sensitive. Conclusion Bisphosphonates can inhibit the proliferation of lung cancer cells and human normal liver cells in different degrees. The inhibiting effect is associated with the kind and concentration of bisphosphonates, and also the kind of lung cancer cells.