School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
Lasers Med Sci. 2021 Mar;36(2):339-347. doi: 10.1007/s10103-020-03035-w. Epub 2020 Jul 5.
This study aims to evaluate the photodynamic efficacy of purpurin 18 (pu-18) on triple negative breast cancer both in vitro and in vivo. Two states of 4T1 cells, 2D culture and 3D spheroids, were used to evaluate the photodynamic action of pu-18 in vitro. The in vitro study results indicated that for the 4T1 2D cell culture, the photodynamic therapy (PDT) treatment showed significant photocytotoxicity at low pu-18 concentrations following light irradiation. Pu-18 was found to distribute on the lysosomes, mitochondria, Golgi apparatus, and endoplasmic reticulum. After irradiation, pu-18 can generate ROS to destroy the mitochondrial membrane potential (MMP) and eventually induce apoptosis in the 2D 4T1 cells. Light-activated pu-18 could also induce the destruction of the 3D 4T1 cell spheroids. The in vivo study was conducted by using a subcutaneous 4T1 breast cancer animal model. The results demonstrated that pu-18 could remain in the tumor for more than 4 days by direct intra-tumoral injection. The PDT treatment was performed every 2 days for a total of 3 times. The results showed that PDT treatment could significantly inhibit tumor growth in vivo, indicating a good photodynamic efficacy of pu-18 in the mouse breast cancer model, without influencing weight and major organ function. The survival pattern results showed that PDT treatment could largely extend the survival time of mice with breast cancer. The preliminary conclusion is that photodynamic treatment using pu-18 is effective at preventing the growth of triple negative breast cancer cells both in vitro and in vivo. A combination of light irradiation and pu-18 could therefore be a worthwhile approach for the treatment of triple negative breast cancer.
本研究旨在评估紫草素 18（pu-18）在体外和体内对三阴性乳腺癌的光动力疗效。使用两种 4T1 细胞状态，即 2D 培养和 3D 球体，来评估 pu-18 的光动力作用。体外研究结果表明，对于 4T1 2D 细胞培养，光动力疗法（PDT）治疗在低 pu-18 浓度下经光照后显示出显著的光细胞毒性。发现 pu-18 分布在溶酶体、线粒体、高尔基体和内质网中。照射后，pu-18 可以产生 ROS 破坏线粒体膜电位（MMP），最终导致 2D 4T1 细胞凋亡。光激活的 pu-18 还可以诱导 3D 4T1 细胞球体的破坏。体内研究通过使用皮下 4T1 乳腺癌动物模型进行。结果表明，直接瘤内注射 pu-18 可使 pu-18 在肿瘤中停留超过 4 天。PDT 治疗每 2 天进行一次，共进行 3 次。结果表明，PDT 治疗可显著抑制体内肿瘤生长，表明 pu-18 在小鼠乳腺癌模型中具有良好的光动力疗效，对体重和主要器官功能无影响。生存模式结果表明，PDT 治疗可大大延长患有乳腺癌的小鼠的生存时间。初步结论是，使用 pu-18 的光动力治疗在体外和体内均能有效抑制三阴性乳腺癌细胞的生长。因此，光照射和 pu-18 的联合使用可能是治疗三阴性乳腺癌的一种有价值的方法。
