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采用低剂量二极管激光联合阿霉素的锌酞菁光动力疗法是人 SK-MEL-3 黑素瘤细胞的协同组合疗法。

Photodynamic therapy using zinc phthalocyanine with low dose of diode laser combined with doxorubicin is a synergistic combination therapy for human SK-MEL-3 melanoma cells.

机构信息

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.

出版信息

Photodiagnosis Photodyn Ther. 2019 Dec;28:88-97. doi: 10.1016/j.pdpdt.2019.08.027. Epub 2019 Aug 24.

DOI:10.1016/j.pdpdt.2019.08.027
PMID:31454716
Abstract

Chemotherapy is a generally used anticancer strategy for melanoma and it may have improved outcomes in combination with other approaches. One such strategy is photodynamic therapy (PDT), where a photosensitizer (PS) generates reactive oxygen species (ROS) after illumination of target cells. Interestingly, in low doses and high doses of light sources, special cellular responses can be induced. Regarding this fact, in this study, the combination of zinc phthalocyanine (ZnPc)-PDT and Doxorubicin (DOX) was applied at low and high dose of diode laser to treat SK-MEL-3 cells. Cytotoxic effects were determined by MTT assay for assessment synergistic effects were estimated by calculation of Combination Index (CI); that synergistic effects were observed in most groups. In low dose of laser irradiation higher synergism effects were observed. Significant changes of ROS were not observed with combinations, but autophagy, subG1 and G2/M phase cell cycle arrest, decreased cell migration ability and apoptosis induction were significantly increased compared to either treatment alone. The expression of caspase-8, -9, -3 and Bcl-2 genes revealed caspase-dependent apoptosis in all groups. Moreover, ZnPc-PDT and chemo-PDT down-regulated the expression of MMP-9 and Vimentin genes that impaired cell migration. In conclusion, it can be suggested that pre-treatment with ZnPc-PDT has high effects to sensitize SK-MEL-3 cells to DOX, in particular with low dose of diode laser.

摘要

化疗是一种常用于治疗黑色素瘤的抗癌策略,它与其他方法联合使用可能会改善治疗效果。一种这样的策略是光动力疗法(PDT),其中光敏剂(PS)在照射靶细胞后会产生活性氧(ROS)。有趣的是,在低剂量和高剂量的光源下,可以诱导特殊的细胞反应。鉴于这一事实,在这项研究中,锌酞菁(ZnPc)-PDT 和阿霉素(DOX)的联合应用于二极管激光的低剂量和高剂量来治疗 SK-MEL-3 细胞。通过 MTT 测定法测定细胞毒性作用,以评估协同作用,并通过计算组合指数(CI)来估计;在大多数组中观察到协同作用。在低剂量激光照射下观察到更高的协同作用。虽然联合治疗并没有观察到 ROS 的显著变化,但与单独治疗相比,自噬、亚 G1 和 G2/M 期细胞周期阻滞、细胞迁移能力下降和凋亡诱导显著增加。Caspase-8、-9、-3 和 Bcl-2 基因的表达显示所有组中都存在 caspase 依赖性凋亡。此外,ZnPc-PDT 和化疗-PDT 下调了 MMP-9 和波形蛋白基因的表达,从而损害了细胞迁移。总之,可以认为 ZnPc-PDT 的预处理对 DOX 增敏 SK-MEL-3 细胞具有高效果,特别是二极管激光的低剂量。

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