Ozturk O H, Bozcuk H, Burgucu D, Ekinci D, Ozdogan M, Akca S, Yildiz M
Akdeniz University, Department of Biochemistry, Antalya, Turkey.
Cell Biol Int. 2007 Sep;31(9):1069-71. doi: 10.1016/j.cellbi.2007.02.004. Epub 2007 Feb 25.
We tested whether zoledronic acid, a biphosphonate with proposed apoptotic activity, augmented the cytotoxicity of cisplatin and/or gemcitabine in A549 lung cancer cell line. This cell line was subjected to different concentrations of the above chemotherapeutic agents and zoledronic acid. Cytotoxicity was assessed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide) assay. Particularly, zoledronic acid in 100 micromolar (microM) concentration augmented the cytotoxicity by cisplatin 1microg/ml from 25% to 70% (Z=3.22, P=0.0072). A significant portion of cells underwent apoptosis with or without zoledronic acid, but more so with the combination treatment as assessed by an Annexin V-FITC apoptosis detection kit. However, 100microM zoledronic acid showed 50% cytotoxicity on its own, but failed to improve cytotoxicity by Gemcitabine. Thus, we show for the first time in a lung cancer cell line that zoledronic acid bears cytotoxic potential on its own and in conjunction with cisplatin. The clinical potential of this finding should be further studied.
我们测试了唑来膦酸（一种具有凋亡活性的双膦酸盐）是否能增强顺铂和/或吉西他滨对A549肺癌细胞系的细胞毒性。该细胞系接受了不同浓度的上述化疗药物和唑来膦酸处理。通过MTT（3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四钠）法评估细胞毒性。具体而言，100微摩尔（μM）浓度的唑来膦酸将1微克/毫升顺铂的细胞毒性从25%提高到了70%（Z=3.22，P=0.0072）。无论有无唑来膦酸，都有相当一部分细胞发生凋亡，但通过膜联蛋白V-异硫氰酸荧光素凋亡检测试剂盒评估发现，联合治疗时凋亡情况更明显。然而，100μM唑来膦酸自身显示出50%的细胞毒性，但未能增强吉西他滨的细胞毒性。因此，我们首次在肺癌细胞系中表明，唑来膦酸自身以及与顺铂联合使用时均具有细胞毒性潜力。这一发现的临床潜力应进一步研究。
