title: Hiporfin-mediated photodynamic therapy in preclinical treatment of osteosarcoma.
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 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.
authors.affiliation: Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Mengxiong
authors.initials: M
authors.lastname: Sun
authors.forename: Chenghao
authors.initials: C
authors.lastname: Zhou
authors.forename: Hui
authors.initials: H
authors.lastname: Zeng
authors.forename: Nahum
authors.initials: N
authors.lastname: Puebla-Osorio
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Damiani
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Wang
authors.forename: Guodong
authors.initials: G
authors.lastname: Li
authors.forename: Fei
authors.initials: F
authors.lastname: Yin
authors.forename: Liancheng
authors.initials: L
authors.lastname: Shan
authors.forename: Dongqing
authors.initials: D
authors.lastname: Zuo
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Liao
authors.forename: Zhuoying
authors.initials: Z
authors.lastname: Wang
authors.forename: Longpo
authors.initials: L
authors.lastname: Zheng
authors.forename: Yingqi
authors.initials: Y
authors.lastname: Hua
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Cai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms / Q000188:drug therapy / Q000628:therapy*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D012516:Osteosarcoma / Q000188:drug therapy / Q000628:therapy*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D017319:Photosensitizing Agents