Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Orthopedic Laboratory of Chongqing Medical University, Chongqing 400016, China.
Photodiagnosis Photodyn Ther. 2022 Mar;37:102646. doi: 10.1016/j.pdpdt.2021.102646. Epub 2021 Nov 21.
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.
光动力疗法（PDT）利用光敏剂与光之间的光化学反应，通过产生活性氧（ROS）来导致癌细胞死亡。X 盒结合蛋白 1（XBP1）是 IRE1α-XBP1 通路的下游产物，调节多种靶基因，包括各种原癌基因，其过表达与恶性肿瘤的发生和发展密切相关。本研究旨在探讨 XBP1 在 MPPα 介导的光动力疗法（MPPα-PDT）（MPPα-PDT）处理的人骨肉瘤 HOS 细胞中的作用及其潜在机制。结果显示，MPPα-PDT 处理后，IRE1α 和 XBP1 蛋白呈时间依赖性增加，表明 MPPα-PDT 诱导了 HOS 细胞中 IRE1α-XBP1 通路的激活。此外，单独用 MPPα-PDT 处理或与 XBP1 敲低联合处理均可抑制细胞活力，但后者的抑制效果更为显著，表明 XBP1 敲低可能通过 MPPα-PDT 增强细胞抑制作用。同时，流式细胞术（FCM）检测到细胞凋亡率显著增加，凋亡蛋白表达增加。此外，当 XBP1 在 MPPα-PDT 下被敲低时，HOS 细胞中的抗氧化相关蛋白，如 Catalase 和 SOD1 蛋白水平降低，而细胞内 ROS 含量增加。这些结果表明，XBP1 介导 HOS 细胞耐药的机制可能与抗氧化分子的表达有关。综上所述，本研究发现 MPPα-PDT 处理后 HOS 细胞中 IRE1α-XBP1 通路被激活，进一步研究表明，XBP1 敲低可通过凋亡降低 HOS 细胞活力，并同时显著增强 MPPα-PDT 的抗肿瘤作用，这与氧化应激系统的调节有关。
