Forsea A-M, Müller C, Riebeling C, Orfanos C E, Geilen C C
1st Clinic of Dermatology, Colentina Hospital, 'Carol Davila' University of Medicine and Pharmacy, Bucharest, Romania.
Br J Cancer. 2004 Aug 16;91(4):803-10. doi: 10.1038/sj.bjc.6602052.
Cutaneous melanoma is one of the highly malignant human tumours, due to its tendency to generate early metastases and its resistance to classical chemotherapy. We recently demonstrated that pamidronate, a nitrogen-containing bisphosphonate, has an antiproliferative and proapoptotic effect on different melanoma cell lines. In the present study, we compared the in vitro effects of three different bisphosphonates on human melanoma cell lines and we demonstrated that the two nitrogen-containing bisphosphonates pamidronate and zoledronate inhibited the proliferation of melanoma cells and induced apoptosis in a dose- and time-dependent manner. Moreover, cell cycle progression was altered, the two compounds causing accumulation of the cells in the S phase of the cycle. In contrast, the nonaminobisphosphonate clodronate had no effect on melanoma cells. These findings suggest a direct antitumoural effect of bisphosphonates on melanoma cells in vitro and further support the hypothesis of different intracellular mechanisms of action for nitrogen-containing and nonaminobisphosphonates. Our data indicate that nitrogen-containing bisphosphonates may be a useful novel therapeutic class for treatment and/or prevention of melanoma metastases.
皮肤黑色素瘤是人类高度恶性肿瘤之一，因其易于早期转移且对传统化疗具有抗性。我们最近证明，含氮双膦酸盐帕米膦酸对不同黑色素瘤细胞系具有抗增殖和促凋亡作用。在本研究中，我们比较了三种不同双膦酸盐对人黑色素瘤细胞系的体外作用，结果表明含氮双膦酸盐帕米膦酸和唑来膦酸以剂量和时间依赖性方式抑制黑色素瘤细胞增殖并诱导细胞凋亡。此外，细胞周期进程发生改变，这两种化合物导致细胞在细胞周期的S期积累。相比之下，非氨基双膦酸盐氯膦酸对黑色素瘤细胞没有影响。这些发现表明双膦酸盐在体外对黑色素瘤细胞具有直接抗肿瘤作用，并进一步支持含氮双膦酸盐和非氨基双膦酸盐具有不同细胞内作用机制的假说。我们的数据表明，含氮双膦酸盐可能是治疗和/或预防黑色素瘤转移的一种有用的新型治疗类别。
