Background:The increased incidence of malignant melanoma is observed in patients with Parkinson’s disease.Methods:The anti-proliferative effects of carbidopa and rasagiline on four human malignant melanoma cell lines (A375, SK-MEL28, FM55P and FM55M2) were determined in MTT assay. The interaction profiles of rasagiline in combinations with cisplatin (CDDP) and mitoxantrone (MTX) in four human melanoma cell lines (A375, SK-MEL28, FM55P and FM55M2) were assessed by means of the isobolographic analysis in the MTT test;Results:Rasagiline, but not carbidopa, produced clear-cut anti-proliferative effects on various melanoma cell lines. The median inhibitory concentrations (IC50values) of rasagiline in the MTT were 280.69 µM for A375, 402.89 µM for SK-MEL28, 349.44 µM for FM55P, and 117.45 µM for FM55M2, respectively. The experimentally-derived selectivity index for rasagiline ranged from 8.22 to 28.18. Flow cytometry assay revealed, in two melanoma cell lines (FM55P and A375), a significant increase in the number of cells in the G0/G1 (up to 76.48% and 75.46% for cell lines, respectively), accompanied by a decrease in the percentage of cells in the S phase (decrease to 9.91% and 10.83% for cell lines, respectively), which may indicate potential cytostatic properties of rasagiline. The combinations of rasagiline with CDDP (at the fixed-ratio of 1:1) exerted either antagonistic interactions (p< 0.05) in the A375 and SK-MEL28, or additive interactions, with a tendency toward antagonism in the FM55P and FM55M2 cell lines in the MTT test. In contrast, the combinations of rasagiline with MTX (ratio of 1:1) produced either synergistic interaction (p< 0.05) in the FM55P cell line or additive interactions with a tendency toward synergy in the FM55M2, SK-MEL28, and A375 cell lines in the MTT test.Conclusions:Rasagiline combined with MTX exerted the most desirable synergistic interactions in relation to the anti-proliferative effects in four malignant melanoma cell lines, as assessed isobolographically. In contrast, rasagiline should not be combined with CDDP during the treatment of malignant melanoma due to the antagonistic interactions in the MTT assay.
背景：帕金森病患者中恶性黑色素瘤的发病率有所增加。方法：通过MTT法测定卡比多巴和雷沙吉兰对四种人恶性黑色素瘤细胞系（A375、SK-MEL28、FM55P和FM55M2）的抗增殖作用。在MTT实验中，采用等效线图分析法评估了雷沙吉兰与顺铂（CDDP）和米托蒽醌（MTX）联合应用时，在四种人黑色素瘤细胞系（A375、SK-MEL28、FM55P和FM55M2）中的相互作用特征。结果：雷沙吉兰（而非卡比多巴）对多种黑色素瘤细胞系产生了明确的抗增殖作用。在MTT实验中，雷沙吉兰对A375、SK-MEL28、FM55P和FM55M2细胞系的半数抑制浓度（IC50值）分别为280.69 µM、402.89 µM、349.44 µM和117.45 µM。实验得出的雷沙吉兰选择性指数范围为8.22至28.18。流式细胞术检测显示，在两种黑色素瘤细胞系（FM55P和A375）中，处于G0/G1期的细胞数量显著增加（分别高达76.48%和75.46%），同时S期细胞百分比下降（分别降至9.91%和10.83%），这可能表明雷沙吉兰具有潜在的细胞抑制作用。在MTT实验中，雷沙吉兰与CDDP（按1:1固定比例）联合使用时，在A375和SK-MEL28细胞系中表现出拮抗作用（p < 0.05），而在FM55P和FM55M2细胞系中则表现为相加作用，但倾向于拮抗。相比之下，雷沙吉兰与MTX（比例为1:1）联合使用时，在FM55P细胞系中产生协同作用（p < 0.05），而在FM55M2、SK-MEL28和A375细胞系中则表现为相加作用，但倾向于协同。结论：根据等效线图分析评估，雷沙吉兰与MTX联合应用在四种恶性黑色素瘤细胞系中产生了最理想的协同抗增殖作用。相反，由于在MTT实验中观察到拮抗作用，雷沙吉兰在治疗恶性黑色素瘤时不应与CDDP联合使用。
肿瘤(癌症)患者之家