1. Hiporfin-Mediated Photodynamic Therapy in Preclinical Treatment of Osteosarcoma.
- Author
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Sun, Mengxiong, Zhou, Chenghao, Zeng, Hui, Puebla ‐ Osorio, Nahum, Damiani, Elisabetta, Chen, Jian, Wang, Hongsheng, Li, Guodong, Yin, Fei, Shan, Liancheng, Zuo, Dongqing, Liao, Yuxin, Wang, Zhuoying, Zheng, Longpo, Hua, Yingqi, and Cai, Zhengdong
- Subjects
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OSTEOSARCOMA , *PHOTODYNAMIC therapy , *CANCER cells , *ANTINEOPLASTIC agents , *APOPTOSIS , *GENE expression , *THERAPEUTICS - Abstract
This study was carried out to investigate the anti-tumor effect and mechanism of hiporfin-mediated photodynamic therapy (hiporfin- PDT) in osteosarcoma. We found that hiporfin accumulated mainly in the cytoplasm of osteosarcoma cells in a time and concentration-dependent manner. Hiporfin- PDT inhibited the proliferation, induced apoptosis and produced cell cycle arrest at G2 M in osteosarcoma cell lines. Hiporfin- PDT increased the expression of cleaved-caspase-3, cleaved PARP-1, Bax and RIP1 while it decreased the expression of Bcl-2; in addition, low concentration of hiporfin increased LC3 conversion. Furthermore, cell death caused by hiporfin- PDT could be rescued by Nec-1 but not by Z- VAD- FMK. Production of reactive oxygen species was increased after hiporfin- PDT. In vivo studies showed a significant decrease in tumor volume and weight after hiporfin- PDT in all three tumor mouse models investigated (subcutaneous and orthotopic). Histological analysis showed widespread cell apoptosis and necrosis after treatment. Immunohistochemistry also showed upregulation of cleaved-caspase-3 and downregulation of Bcl-2 after hiporfin- PDT. These results indicate that hiporfin- PDT exhibits a killing effect in osteosarcoma both in vitro and in vivo, which is associated with apoptosis and necroptosis, while autophagy plays a protective role. All these findings shed light on a potential future clinical use for hiporfin in the treatment of osteosarcoma. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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