竹红菌乙素光诱导A549细胞凋亡的机制研究

Study on the Mechanism of Light-induced A549 Cell Apoptosis by Hypocrellin B

竹红菌乙素(HB)在特定波长照射下可有效杀伤多种癌细胞,但其光诱导细胞死亡的机制尚未完全阐明。为了探索竹红菌乙素(HB)光诱导人肺腺癌细胞A549细胞死亡的机制,本研究运用激光扫描共聚焦显微镜、MTT染色法、流式细胞技术及蛋白质印迹(Western blot)等技术,针对HB在A549中细胞摄取、亚细胞定位、细胞内活性氧的生成、细胞毒性以及细胞死亡机制,进行了详细评估。研究结果显示,HB能够选择性地定位在线粒体,对A549细胞具有较低的暗毒性和较高的光毒性。HB能够光诱导线粒体损伤、线粒体膜电位改变、线粒体内细胞色素c释放和半胱天冬酶的激活,最终引发A549细胞凋亡。由此可见,天然产物HB作为一种靶向线粒体的潜在光敏剂,具有优异的抗肿瘤活性,可通过线粒体介导的内源途径信号通路诱导细胞凋亡。通过该研究,为HB光动力治疗非小细胞肺癌的临床应用提供参考和理论依据。

Hypocrellin B(HB)can effectively eliminate a variety of cancer cells under specific wavelength irradiation,but the mechanism of light-induced cell death has not been fully elucidated.To study the mechanism of light-induced cell death in human lung adenocarcinoma cells(A549 cells),we evaluated the cellular uptake,subcellular localization,intracellular reactive oxygen species production,cytotoxicity,and apoptosis mechanism of HB in A549 cells by using laser confocal microscopy,MTT staining,flow cytometry and Western blot.The results show that HB could be selectively target mitochondria and had low dark toxicity and high phototoxicity to A549 cells.HB can light-induced mitochondrial damage,mitochondrial membrane potential change,cytochrome c release,and caspase activation in mitochondria,which eventually leads to apoptosis of A549 cells.These results indicate that natural product HB,as a potential mitochondria-targeting photosensitizer,exhibits excellent anticancer activity,and can induce cell apoptosis through mitochondrial-mediated endogenous pathway signaling pathways.This study provides a reference and theoretical basis for the clinical photodynamic therapy of non-small cell lung cancer by using HB.