2. Academic Validation
  3. Targeting X box-binding protein-1 (XBP1) enhances the sensitivity of HOS osteosarcoma cells to pyropheophorbide- α methyl ester-mediated photodynamic therapy

Targeting X box-binding protein-1 (XBP1) enhances the sensitivity of HOS osteosarcoma cells to pyropheophorbide- α methyl ester-mediated photodynamic therapy

  • Photodiagnosis Photodyn Ther. 2022 Mar;37:102646. doi: 10.1016/j.pdpdt.2021.102646.
Haoyang Yu 1,  Ye Zhang 2,  Qiang Zuo 3,  Shenxi Zhong 4,  Yanyang Chen 5,  Muzi Zhang 6,  Fangbiao Zhan 7,  Yunsheng Ou 8
Affiliations

Affiliations

  • 1 Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Orthopedic Laboratory of Chongqing Medical University, Chongqing 400016, China. Electronic address: yuhaoyang20201003@163.com.
  • 2 Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Orthopedic Laboratory of Chongqing Medical University, Chongqing 400016, China. Electronic address: 497802217@qq.com.
  • 3 Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Orthopedic Laboratory of Chongqing Medical University, Chongqing 400016, China. Electronic address: zqcyxy@sina.com.
  • 4 Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Orthopedic Laboratory of Chongqing Medical University, Chongqing 400016, China. Electronic address: 252835356@qq.com.
  • 5 Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Orthopedic Laboratory of Chongqing Medical University, Chongqing 400016, China. Electronic address: chenyanyang_007@163.com.
  • 6 Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Orthopedic Laboratory of Chongqing Medical University, Chongqing 400016, China. Electronic address: 513010209@qq.com.
  • 7 Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Orthopedic Laboratory of Chongqing Medical University, Chongqing 400016, China. Electronic address: zhanfangbiao@bjmu.edu.cn.
  • 8 Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Orthopedic Laboratory of Chongqing Medical University, Chongqing 400016, China. Electronic address: ouyunsheng2001@163.com.
PMID: 34818599 DOI: 10.1016/j.pdpdt.2021.102646
Abstract

Photodynamic therapy (PDT), utilizes a photochemical reaction between photosensitizer and light to cause Cancer death by generating Reactive Oxygen Species (ROS). X-box binding protein 1 (XBP1), a downstream product of the IRE1α-XBP1 pathway, regulates diverse target genes, including various proto-oncogenes and its overexpression was closely related to the occurrence and progression of malignant tumors. The present study was performed to explore the role of XBP1 in human osteosarcoma HOS cells treated with pyropheophorbide-α methyl ester (MPPα)-mediated photodynamic therapy (PDT) (MPPα-PDT) and its potential mechanisms. The protein IRE1α and XBP1 increased with a time-dependent manner after MPPα-PDT treated, which indicated that MPPα-PDT induced the activation of the IRE1α-XBP1 pathway in HOS cells. Besides, MPPα-PDT treated alone or combined with XBP1 knockdown could both restrain the cell viability, but the latter one has more notable effect, which indicated that XBP1 knockdown may enhance the cell inhibitory effect by MPPα-PDT. Simultaneously, the apoptotic rate measured by flow cytometry (FCM) was increased surprisedly and the expression of Apoptosis proteins was increased when knockdown XBP1 under the MPPα-PDT. In addition, antioxidant-related proteins such as the Catalase and SOD1 protein levels decreased, while the intracellular ROS content increased in HOS cells when knockdown XBP1 under the MPPα-PDT. These results suggested that the mechanism of XBP1 mediating resistance in HOS cells might be related to the expression of antioxidant molecules. In summary, this study found that the IRE1α-XBP1 pathway was activated in HOS cells after MPPα-PDT treated, and furthermore, XBP1 knockdown could decrease HOS cell viability through Apoptosis and enhance the anti-tumor effect of MPPα-PDT remarkably in the meantime, which related to the regulation of oxidation-antioxidant system.

Keywords

Osteosarcoma; Photodynamic therapy; Pyropheophorbide-α methyl ester; X-box binding protein 1.

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