金属卟啉化合物对人前列腺癌细胞PC-3的光动力杀伤作用

Effect of Photodynamic Therapy with Metalloporphyrin Compound on Human Prostate Cancer PC-3 Cells in vitro

目的:研究水溶性金属卟啉化合物对人前列腺癌细胞PC 3的光动力学杀伤作用,探讨金属卟啉的光动力 学杀伤作用抗肿瘤的机制。 方法:合成水溶性金属卟啉化合物5,10,15,20 四(N 甲基 4 吡啶基)锰卟啉四碘盐 后,采用四甲基偶氮唑蓝比色法和膜联蛋白/碘化丙锭双标记流式细胞术分别检测不同浓度的金属锰卟啉化合物 (0、0.1、1、10μmol/L)在不同时间(0、15、30、45min)的高压汞灯(40W)照射下,对PC 3细胞的生长活性和凋亡的 影响。 结果:锰卟啉浓度在0～10μmol/L、光照0～30min范围内,其对PC 3细胞的增值抑制作用和诱导PC 3 细胞的凋亡作用均随着浓度增加和光照时间的增加而增强,但大剂量(10μmol/L)、高能量照射(光照45min)时主 要导致PC 3细胞坏死。 结论:水溶性金属卟啉化合物5,10,15,20 四(N 甲基 4 吡啶基)锰卟啉四碘盐的光动 力作用在体外能诱导PC 3细胞凋亡,有效杀伤PC 3细胞,其杀伤效果在锰卟啉浓度为0～10μmol/L、光照0～30 min范围内与锰卟啉的浓度和光照射剂量呈正相关,这可能是卟啉的光动力学疗法抗肿瘤作用的机制。

Objective: To investigate the effect of the photodynamic therapy(PDT) with the new water-soluble metalloporphyrin compound on human prostate cancer PC-3 cells in vitro and the anticancer mechanism of PDT. Methods: The new water-soluble manganese, 5,10,15,20-tetra (N-methyl-4-pyridyl) porphinato (2-) tetraiodide salt, was synthesized. The PC-3 cells were treated with the compound of serial concentrations( 0, 0.1, 1, 1.0 μmol/L) followed by irradiation of different dosages of visible light. The techniques of MTT and Annexin-V/propidium iodide double-labeled flow cytometry (FCM) were applied to measuring the inhibitory effect of the compound on the growth activity and apoptosis of the cells. Results: When the metalloporphyrin compound concentration was within 10 μmol/L and the irradiation time was within 30 min, the water-soluble metalloporphyrin compound had a significant inhibitory effect on the proliferation of PC-3 cells and induced PC-3 cell apoptosis, and the effects depended greatly on metalloporphyrin concentration and illumination dosages. Higher concentrations and dosages induced the death of the majority of PC-3 cells. Conclusion: The PDT of the water-soluble metalloporphyrin compound followed by light irradiation has a distinctive killing effect on PC-3 cells in vitro, and the rates of proliferation inhibition and cell apoptosis are correlated with metalloporphyrin concentration and the dosages of light irradiation. The results suggest that the mechanism of metalloporphyrin PDT may be involved with the induction of apoptosis in human prostate cancer cells.