Sulfasalazine increases the radiosensitivity of colorectal cancer cells by promoting ferroptosis
Li Meng1, Li Chan1, Chen Yao1, Pan Haixia2, Jin Tao1, Tian Shumei1, Zhao Gang3, Xie Ke2
1Department of Oncology, People's Hospital of Xinjin, Chengdu, Chengdu 611430, China; 2Department of Oncology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu 610031, China; 3Lab of Experimental Oncology, West China Hospital of Sichuan University, Chengdu 610041, China
Abstract：Objective To investigate the radiosensitization effect of low‐dose sulfasalazine (SAS) on colorectal cancer (CRC) cells. Methods Proliferation inhibition effect of SAS on CRC cells was detected by CCK‐8 assay, and the concentration of SAS in vitro assays was based on its IC10 value. CRC cells were treated with SAS alone or combined with inhibitors of apoptosis, autophagy, ferroptosis and necroptosis, then cell viability was detected by CCK‐8 assay. Trypan blue staining, clone formation assay and cell growth curves were used to verify the radiosensitization effect of SAS on CRC cells in vitro. CRC cells were treated with SAS and radiotherapy, then the intracellular contents of lipid peroxidation and the protein levels of GPX4, PTGS2, cleaved PARP and active caspase 3 were evaluated, respectively. Subcutaneous xenograft tumor mouse model was established to further verify the radiosensitization effect of SAS in vivo. Results High dose (lethal dose) of SAS could induce apoptosis and ferroptosis in CRC cells. Low dose (non‐lethal dose) of SAS enhanced the radiosensitivity of CRC cells in vitro, and the radiosensitivity effect of SAS could only be abolished by ferroptosis inhibitor (Fer‐1). Low dose of SAS combined with radiotherapy significantly down‐regulated the expression of GPX4, whereas increased the intracellular lipid peroxidation levels and the expression of PTGS2. SAS also showed significant radiosensitization effect in subcutaneous xenograft tumor model. Conclusion Our findings suggest that low‐dose SAS could increase the radiosensitivity of CRC cells by promoting ferroptosis.
Li Meng,Li Chan,Chen Yao et al. Sulfasalazine increases the radiosensitivity of colorectal cancer cells by promoting ferroptosis[J]. Chinese Journal of Radiation Oncology, 2022, 31(8): 727-731.
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