Pheophorbide a-Mediated Photodynamic Therapy Triggers HLA Class I-Restricted Antigen Presentation in Human Hepatocellular Carcinoma
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摘要The immunomodulatory effects of photodynamic therapy (PDT) have been reported in several photosensitizers. Pheophorbide a (Pa), a chlorophyll derivative, shows antitumor effects on a number of human cancers in a PDT approach (Pa-PDT); however, the potential effect of Pa-PDT on the anticancer immunity has never been studied. In the present work, the underlying action mechanism of Pa-PDT was systemically investigated with a human hepatoma cell line HepG2. We found that Pa-PDT significantly inhibited the growth of HepG2 cells with a half maximal inhibitory concentration/endoplasmic reticulum of 0.35 mu M at 24 hours by the induction of apoptosis, as shown by externalization of phosphatidylserine, release of mitochondrial cytochrome c, and activation of the caspases cascade in the treated cells. Interestingly, using two-dimensional polyacrylamide gel electrophoresis analysis, a 57-kDa disulfide-isomerase-like ER resident protein (ERp57) that belongs to the HLA class I-restricted antigen-processing machinery was found to be mediated during the Pa-PDT treatment. This activation of antigen presentation was confirmed by Western blot analysis and immunostaining. Furthermore, a cross-presentation of antigen with HLA class I proteins and 70-kDa heat shock protein was found in Pa-PDT-treated cells, as shown by the confocal microscopic observation and immunoprecipitation assay. Nevertheless, the immunogenicity of HepG2 cells was increased by Pa-PDT treatment that triggered phagocytic capture by human macrophages. Our findings provide the first evidence that Pa-PDT can trigger both apoptosis and cancer immunity in the tumor host.
著者Tang PMK, Bui-Xuan NH, Wong CK, Fong WP, Fung KP
期刊名稱Translational Oncology
出版年份2010
月份4
日期1
卷號3
期次2
出版社NEOPLASIA PRESS
頁次114 - 122
國際標準期刊號1944-7124
語言英式英語
Web of Science 學科類別Oncology; ONCOLOGY

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