首页> 中文期刊> 《中国肿瘤临床》 >癌光啉对人乳腺癌细胞MDA-MB-231的光动力杀伤效应及其机制研究

癌光啉对人乳腺癌细胞MDA-MB-231的光动力杀伤效应及其机制研究

             

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Objective: This study aims to evaluate the efficacy of carcinophotorin (PSD-007) photosensitization on the apopto-sis-induced response in human breast cancer cells and analyze the mechanisms of PSD-007 involved in this process. Methods: Methyl thiazolyl tetrazolium (MTT) assay and in situ labeling were performed to examine the effects of the photodynamic therapy (PDT) on the proliferation and apoptosis of the cancer cells MDA-MB-231, respectively. Changes in cellular morphology were assessed using an optical microscope. Real-time polymerase chain reaction and Western blot analysis were conducted to clarify the underlying mecha-nisms. Results: The MTT assay revealed that at a concentration of 10 μg/mL and in combination with 9.0 J/cm2 laser radiation power 24 h after cell culture, PSD-007 markedly inhibited the proliferation of breast tumor cells, with an inhibition rate of 97.01%." Under a fluorescent microscope, apoptotic cells in the treatment groups with 5 and 10 μg/mL PSD-007-PDT were observed to have dramatically outnumbered the control groups. The dead cells after PSD-007-PDT mainly consisted of necrotic and late apoptotic cells. Caspase-3, caspase-8, P65, and P53 expression was upregulated in the treatment groups compared with the control group, with 5 and 10 μg/ml PSD-007 therapies, whereas no significant alteration in Bcl-2 and Bcl-x was found. Conclusion: PDT inhibits the proliferation and in-duces the apoptosis of cancer cells MDA-MB-231 by upregulating the caspase-3, caspase-8, P53, and NF-KB pathways, indicating a new strategy for treating breast cancer in the future.%  目的:探讨癌光啉(PSD-007)在体外对于乳腺癌细胞株MDA-MB-231光动力杀伤效应,并分析其分子机制.方法:MTT法检测不同浓度PSD-007(0、2、4、6、8、10μg/mL)作用于MDA-MB-231细胞株后对其增殖的影响;光学显微镜下观察光动力治疗后细胞形态的变化,荧光显微镜分析PSD-007作用后细胞的死亡形式.应用RT-PCR和Western blotting技术分析其分子机制.结果:当PSD007浓度为10μg/mL、光照能量为9.0 J/cm2时,对乳腺癌细胞的光动力杀伤效应最大,抑制率为97.01%.光动力治疗处理后的细胞逐渐变圆,体积变小,核质比增大,折光性减弱,贴壁能力下降,细胞间隙增大,直到细胞漂浮死亡.荧光显微镜分析结果显示,光动力治疗后死亡细胞主要为坏死或晚期的凋亡细胞.RT-PCR 和Western blot结果显示相比对照组,实验组 Caspase3、Caspase8、P65亚基和 P53表达水平明显上调,而 Bcl-2和 Bcl-x 表达无明显改变.结论:PSD-007在体外通过调控Caspase蛋白酶、P53、NF-KB通路对人乳腺癌MDA-MB-231细胞具有光动力杀伤效应,可能成为未来乳腺癌治疗的一个新方式.

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