Photodynamic Therapy Using a Novel Phosphorus Tetraphenylporphyrin Induces an Anticancer Effect via Bax/Bcl-xL-related Mitochondrial Apoptosis in Biliary Cancer Cells
Photodynamic Therapy Using a Novel Phosphorus Tetraphenylporphyrin Induces an Anticancer Effect via Bax/Bcl-xL-related Mitochondrial Apoptosis in Biliary Cancer Cells
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DOI：
10.1267/ahc.20-00002
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发表时间：
2020-01-01
影响因子：
2.4
通讯作者：
Hishikawa, Yoshitaka
中科院分区：
文献类型：
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作者：
Nguyen Nhat Huynh Mai;Yamaguchi, Yuya;Hishikawa, Yoshitaka
光动力疗法（PDT）利用特定波长的光激活光敏剂，是一种很有前途的治疗各种癌症的方法；然而，PDT的具体机制尚不清楚。因此，我们利用新型磷四苯基卟啉（Ptpp）与发光二极管（Ptpp-PDT）联合对NOZ人胆道癌细胞的抗癌作用进行了研究。采用MTT法、流式细胞术和TUNEL法检测pppp - pdt后24小时细胞活力和凋亡情况。MitoTracker和JC-1作为线粒体定位和膜电位的标记物。western blotting和免疫组织化学检测线粒体氧化磷酸化（OXPHOS）复合物、Bcl-2家族蛋白、细胞色素c和cleaved caspase-3的水平。结果表明，Ptpp定位于线粒体，并且Ptpp- pdt以剂量和时间依赖的方式有效降低细胞活力。在Ptpp-PDT后6 ~ 24小时，JC-1和OXPHOS复合物减少，但凋亡细胞增加。在Ptpp-PDT后6 - 24小时，Bcl-xL降低，Bax、细胞色素c和cleaved caspase-3升高。基于以上结果，我们认为Ptpp-PDT通过改变Bax/Bcl-xL比值，通过线粒体凋亡途径诱导抗癌作用，可能是治疗胆道癌的有效药物。
Photodynamic therapy (PDT) uses photosensitizer activation by light of a specific wavelength, and is a promising treatment for various cancers; however, the detailed mechanism of PDT remains unclear. Therefore, we investigated the anticancer effect of PDT using a novel phosphorus tetraphenylporphyrin (Ptpp) in combination with light emitting diodes (Ptpp-PDT) in the NOZ human biliary cancer cell line. Cell viability and apoptosis were examined by MTT assay, flow cytometry and TUNEL assay for 24 hr after Ptpp-PDT. MitoTracker and JC-1 were used as markers of mitochondrial localization and membrane potential. The levels of mitochondrial oxidative phosphorylation (OXPHOS) complexes, Bcl-2 family proteins, cytochrome c and cleaved caspase-3 were examined by western blotting and immunohistochemistry. The results revealed that Ptpp localized to mitochondria, and that Ptpp-PDT efficiently decreased cell viability in a dose- and time-dependent manner. JC-1 and OXPHOS complexes decreased, but apoptotic cells increased from 6 to 24 hr after Ptpp-PDT. A decrease in Bcl-xL and increases in Bax, cytochrome c and cleaved caspase-3 were also found from 6 to 24 hr after Ptpp-PDT. Based on these results, we conclude that Ptpp-PDT induces anticancer effects via the mitochondrial apoptotic pathway by altering the Bax/Bcl-xL ratio, and could be an effective treatment for human biliary cancer.