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Effect of hyperthermia on biological behavior of squamous cell carcinoma of the tongue by regulating ferroptosis pathway
Shen Pei1,2, Hao Yuli2, Zhou Xuexiao3, Cong yuan1,2, Wang Shengzhi2, Shao yun1,2, Xu Ting2, Li Shouyi2
1School of Stomatology of Qingdao University, Qingdao 266003, China; 2Department of Stomatology, Yantai Yuhuangding Hospital Affiliated to Qingdao University, Yantai 264099, China; 3Department of Dental Implantology, Hospital of Stomatology Sichuan University, Chengdu 610044, China
AbstractObjective To investigate the regulation and possible mechanism of hyperthermia (HT) on the ferroptosis of squamous cell carcinoma of the tongue cell line CAL‐27. Methods Half maximal inhibitory concentration (IC50) of Fer‐1, an inhibitor of ferroptosis, was detected by CCK‐8 assay and used for subsequent experiments. CAL‐27 cells were divided into the HT, control, Fer‐1 and HT+ Fer‐1 groups according to experimental design. Reactive oxygen species (ROS) levels and iron ion concentration were determined by corresponding detection kits. The p53 and TfR1 mRNA levels were detected by real‐time reverse transcription PCR. Cell migration was detected by cell scratch test and cell apoptosis was detected by flow cytometry. Results HT significantly up‐regulated the ROS levels (P<0.01) and iron ion concentration (P<0.001), and significantly increased the expression levels of p53 and TfR1 mRNA (both P<0.01). The cell migration ability was decreased (P<0.001), whereas cell apoptosis rate was increased by HT (P<0.01). In the HT+Fer‐1 group, the ROS levels (P<0.001), iron ion concentration (P<0.001), expression levels of p53 and TfR1 mRNA (both P<0.01) were significantly down‐regulated, the cell migration ability was recovered (P<0.01), and cell apoptosis rate was decreased (P<0.01) compared with those in the HT group, respectively. Conclusions HT may induce the ferroptosis of CAL‐27 cell line, inhibit cell migration ability and promote cell apoptosis by activating the p53/TfR1 pathway.
Fund:Yantai Science and Technology Innovation Development Plan Project (2022YD021)
Corresponding Authors:
Wang Shengzhi, Email: Wangsz916@163.com; Li Shouyi, Email: shouyi516@163.com
Cite this article:
Shen Pei,Hao Yuli,Zhou Xuexiao et al. Effect of hyperthermia on biological behavior of squamous cell carcinoma of the tongue by regulating ferroptosis pathway[J]. Chinese Journal of Radiation Oncology, 2023, 32(3): 260-264.
Shen Pei,Hao Yuli,Zhou Xuexiao et al. Effect of hyperthermia on biological behavior of squamous cell carcinoma of the tongue by regulating ferroptosis pathway[J]. Chinese Journal of Radiation Oncology, 2023, 32(3): 260-264.
[1] Gavazzi S, van Lier A, Zachiu C, et al. Advanced patient-specific hyperthermia treatment planning[J]. Int J Hyperthermia, 2020,37(1):992-1007. DOI: 10.1080/02656736.2020.1806361. [2] van Driel WJ, Koole SN, Sikorska K, et al. Hyperthermic intraperitoneal chemotherapy in ovarian cancer[J]. N Engl J Med, 2018,378(3):230-240. DOI: 10.1056/NEJMoa1708618. [3] Salvador D, Bastos V, Oliveira H.Hyperthermia enhances doxorubicin therapeutic efficacy against A375 and MNT-1 melanoma cells[J]. Int J Mol Sci, 2021,23(1):35. DOI: 10.3390/ijms23010035. [4] Dixon SJ, Lemberg KM, Lamprecht MR, et al.Ferroptosis: an iron-dependent form of nonapoptotic cell death[J]. Cell, 2012,149(5):1060-1072. DOI: 10.1016/j.cell.2012.03.042. [5] Tang LJ, Zhou YJ, Xiong XM, et al.Ubiquitin-specific protease 7 promotes ferroptosis via activation of the p53/TfR1 pathway in the rat hearts after ischemia/reperfusion[J]. Free Radic Biol Med, 2021,162:339-352. DOI: 10.1016/j.freeradbiomed.2020.10.307. [6] Shen Y, Li X, Dong DD, et al.Transferrin receptor 1 in cancer: a new sight for cancer therapy[J]. Am J Cancer Res, 2018,8(6):916-931. [7] An P, Gao Z, Sun K, et al.Photothermal-enhanced inactivation of glutathione peroxidase for ferroptosis sensitized by an autophagy promotor[J]. ACS Appl Mater Interfaces, 2019,11(46):42988-42997. DOI: 10.1021/acsami.9b16124. [8] Kassis S, Grondin M, Averill-Bates DA.Heat shock increases levels of reactive oxygen species, autophagy and apoptosis[J]. Biochim Biophys Acta Mol Cell Res, 2021,1868(3):118924. DOI: 10.1016/j.bbamcr.2020.118924. [9] Luo Z, Zheng KX, Fan Q, et al.Hyperthermia exposure induces apoptosis and inhibits proliferation in HCT116 cells by upregulating miR-34a and causing transcriptional activation of p53[J]. Exp Ther Med, 2017,14(6):5379-5386. DOI: 10.3892/etm.2017.5257. [10] Chen X, Kang R, Kroemer G, et al.Broadening horizons: the role of ferroptosis in cancer[J]. Nat Rev Clin Oncol, 2021,18(5):280-296. DOI: 10.1038/s41571-020-00462-0. [11] Ivanov SD, Semenov AL, Kovan'ko EG, et al. Effects of iron ions and iron chelation on the efficiency of experimental radiotherapy of animals with gliomas[J]. Bull Exp Biol Med, 2015,158(6):800-803. DOI: 10.1007/s10517-015-2865-1. [12] Lin RY, Zhang ZH, Chen LF, et al.Dihydroartemisinin (DHA) induces ferroptosis and causes cell cycle arrest in head and neck carcinoma cells[J]. Cancer Lett, 2016,381(1):165-175. DOI: 10.1016/j.canlet.2016.07.033. [13] Roh JL, Kim EH, Jang HJ, et al.Induction of ferroptotic cell death for overcoming cisplatin resistance of head and neck cancer[J]. Cancer Lett, 2016,381(1):96-103. DOI: 10.1016/j.canlet.2016.07.035. [14] Li TY, Kon N, Jiang L, et al.Tumor suppression in the absence of p53-mediated cell-cycle arrest, apoptosis, and senescence[J]. Cell, 2012,149(6):1269-1283. DOI: 10.1016/j.cell.2012.04.026. [15] Jiang L, Kon N, Li TY, et al.Ferroptosis as a p53-mediated activity during tumour suppression[J]. Nature, 2015,520(7545):57-62. DOI: 10.1038/nature14344. [16] Cheung EC, Vousden KH.The role of ROS in tumour development and progression[J]. Nat Rev Cancer, 2022,22(5):280-297. DOI: 10.1038/s41568-021-00435-0.