5-氨基酮戊酸光動力治療誘導人類口腔癌細胞凋亡機轉之研究
Mechanisms of 5-Aminolevulinic Acid Photodynamic Therapy Induced apoptosis in Oral Carcinoma Cells
Date Issued
2007
Date
2007
Author(s)
Chang, Chih-Wei
DOI
zh-TW
Abstract
Photodynamic therapy (PDT) is a kind of new developing treatment for cancer. 5-Aminolevulinic acid (ALA) is a novel photosensitizer for photodynamic therapy. We previously showed ALA-PDT can induce cytotoxicity in oral cancer cells, however, the mechanism(s) for the ALA-PDT induced cytotoxicity is still unknown. In this study, we demonstrated that ALA-PDT induces apoptosis in human oral cancer cell lines Ca9-22 as evidenced by release of cytochrome C and cleavage of PARP. Apoptosis induced by ALA-PDT was both time- and dose-dependent. Western blot analysis showed ALA-PDT treatment induced FADD, caspase-8 and -9 activations. In addition, ALA-PDT treatment induced reactive oxygen species (ROS) production as detected by DCF fluorescence. Pretreatment of cells with imidazole (singlet oxygen inhibitor) reduced the ALA-PDT-induced apoptosis. These results indicated that singlet oxygen was an important mechanism for ALA-PDT-induced apoptosis in Ca9-22 cells. ALA-PDT-induced apoptosis was also inhibited in the presence of caspase 8 or caspase 9 inhibitors (Z-LEHD-FMK, Z-IETD-FMK). We also found that ALA-PDT was able to induced JNK activation and pretreatment of cells with SP600125 (JNK inhibitor) inhibited ALA-PDT-induced FADD activation, cytochrome C release and PARP cleavage. Pretreatment of cells with Bay (NF-κB inhibitor) inhibited ALA-PDT-induced JNK activation and apoptosis.Taking together, this study showed that ALA-PDT can induce apoptosis in Ca9-22 cells via activating intrinsic- and extrinsic-apoptosis pathway, and the activating of NF-κB and subsequent JNK activation are critical for the initiation of the apoptotic processes.
Subjects
光動力治療
5-氨基酮戊酸
細胞凋亡
口腔癌
photodynamic therapy
5-aminolevulinic acid
apoptosis
oral carcinoma
SDGs
Type
other
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