Yang De-Ming, Chi Chin-Wen, Chang Hwey-May, Wu Li-Hwa, Lee Ting-Kuei, Lin Jen-Der, Chen Szu-Tah, Lee Chen-Hsen
Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China.
Anticancer Res. 2004 May-Jun;24(3a):1617-23.
Clodronate, one of the halogenated bisphosphonates, was found to inhibit the cell growth of endocytic macrophages, osteoclasts and several cancer cells through diverse mechanisms. Cytosolic Ca2+ signaling had previously been suggested as an apoptotic signal to certain cancer cells. Whether clodronate has an anti-cancer effect and induces the Ca2+ signal in thyroid cancer cells remains unknown. In this study, the effects of clodronate, including growth inhibition and cytosolic Ca2+ signaling, were examined and analyzed on ARO, SW579, WRO and TT thyroid cancer cell lines. Clodronate decreased the growth of these cells in a dose-dependent manner and was more effective on slow growing cells. Clodronate treatment transiently increased cytosolic Ca2+ on slow growing SW579 thyroid cancer cells but not on the fast growing ARO cells. The results from this study implied that clodronate-mediated cell growth inhibition in slow growing thyroid cancer cells might correlate with a Ca2+ signaling pathway.
氯膦酸盐是卤代双膦酸盐之一，已发现它可通过多种机制抑制内吞巨噬细胞、破骨细胞和几种癌细胞的细胞生长。此前有人提出胞质Ca2+信号是某些癌细胞的凋亡信号。氯膦酸盐是否具有抗癌作用并在甲状腺癌细胞中诱导Ca2+信号尚不清楚。在本研究中，检测并分析了氯膦酸盐对ARO、SW579、WRO和TT甲状腺癌细胞系的影响，包括生长抑制和胞质Ca2+信号。氯膦酸盐以剂量依赖的方式降低了这些细胞的生长，并且对生长缓慢的细胞更有效。氯膦酸盐处理使生长缓慢的SW579甲状腺癌细胞中的胞质Ca2+短暂增加，但对生长迅速的ARO细胞则没有作用。本研究结果表明，氯膦酸盐介导的生长缓慢的甲状腺癌细胞生长抑制可能与Ca2+信号通路相关。
