Hiporfin-mediated photodynamic therapy in preclinical treatment of osteosarcoma
| Autor: | Ying-qi Hua, Longpo Zheng, Hui Zeng, Mengxiong Sun, Jian Chen, Guodong Li, Chenghao Zhou, Elisabetta Damiani, Dongqing Zuo, Zhuoying Wang, Fei Yin, Yuxin Liao, Hongsheng Wang, Liancheng Shan, Nahum Puebla-Osorio, Zhengdong Cai |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Programmed cell death
Necrosis Necroptosis Apoptosis Bone Neoplasms Biology Biochemistry Mice Downregulation and upregulation In vivo Cell Line Tumor medicine Animals Humans Physical and Theoretical Chemistry Cell Proliferation Osteosarcoma Photosensitizing Agents Autophagy Cell Cycle General Medicine medicine.disease Gene Expression Regulation Neoplastic Disease Models Animal Photochemotherapy Immunology Cancer research medicine.symptom |
| Zdroj: | Photochemistry and photobiology. 91(3) |
| ISSN: | 1751-1097 |
| Popis: | 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 G2M 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text