Abdulrehman Gulinur, Xv Kaiyue, Li Yuhua, Kang Ling
College of Public Health, Xinjiang Medical University, No. 393, Xinyi Road, Xinyi District, Urumqi, Xinjiang, China.
Lasers Med Sci. 2018 Sep;33(7):1581-1590. doi: 10.1007/s10103-018-2524-7. Epub 2018 May 24.
The aim of this study is to investigate the antitumor effects and possible mechanisms of meta-tetrahydroxyphenylchlorin-mediated photodynamic therapy (m-THPC-PDT) on human primary (SW480) and metastatic (SW620) colon cancer cell lines. SW480 and SW620 cells were incubated with various concentrations of m-THPC, followed by photodynamic irradiation. Subcellular localization of m-THPC in cells was observed with confocal laser scanning microscopy (CLSM). Photocytotoxicity of m-THPC in the two cells was investigated by using MTT assay. The flow cytometry was employed to detect the cell apoptosis. The migration and long-term recovery ability were determined by scratch test and colony formation assay respectively. CLSM showed that m-THPC was mainly distributed within the endoplasmic reticulum (ER) and lysosome of SW480 cells and within the lysosome and mitochondria of SW620 cells. m-THPC-PDT induced a dose-dependent and light energy-dependent cytotoxicity in SW480 and SW620 cells. Apoptosis rate was approximately 65 and 25% in SW480 and SW620 respectively when the concentration of m-THPC increased to 11.76 μM. However, the rate of necrotic cells had no significant changes in two cell lines. The colony formation and migration ability of the two cell lines were decreased with m-THPC-PDT treatment in a dose-dependent manner. PDT with m-THPC not only could effectively inhibit cell proliferation and decrease migration ability and colony formation ability, but also could effectively kill SW480 and SW620 cells in a dose-dependent manner in vitro. These results suggest that m-THPC is a promising sensitizer that warrants further development and extensive studies towards clinical use of colorectal cancer.
本研究旨在探讨间-四羟基苯基氯卟啉介导的光动力疗法（m-THPC-PDT）对人原发性（SW480）和转移性（SW620）结肠癌细胞系的抗肿瘤作用及可能机制。将SW480和SW620细胞与不同浓度的m-THPC孵育，随后进行光动力照射。用共聚焦激光扫描显微镜（CLSM）观察m-THPC在细胞内的亚细胞定位。采用MTT法研究m-THPC对这两种细胞的光细胞毒性。运用流式细胞术检测细胞凋亡。分别通过划痕试验和集落形成试验测定细胞迁移和长期恢复能力。CLSM显示，m-THPC主要分布在SW480细胞的内质网（ER）和溶酶体以及SW620细胞的溶酶体和线粒体中。m-THPC-PDT在SW480和SW620细胞中诱导出剂量依赖性和光能依赖性细胞毒性。当m-THPC浓度增加到11.76 μM时，SW480和SW620细胞的凋亡率分别约为65%和25%。然而，两种细胞系中坏死细胞的比例没有显著变化。m-THPC-PDT处理后，两种细胞系的集落形成和迁移能力均呈剂量依赖性降低。m-THPC光动力疗法不仅能有效抑制细胞增殖、降低迁移能力和集落形成能力，还能在体外以剂量依赖性方式有效杀死SW480和SW620细胞。这些结果表明，m-THPC是一种有前景的光敏剂，值得进一步开发并针对结直肠癌的临床应用进行广泛研究。
