4.6 Article

IFNgamma-inducible CXCL10/CXCR3 axis alters the sensitivity of HEp-2 cells to ionizing radiation

Journal

EXPERIMENTAL CELL RESEARCH
Volume 398, Issue 1, Pages -

Publisher

ELSEVIER INC
DOI: 10.1016/j.yexcr.2020.112382

Keywords

IFNgamma; CXCL10; CXCR3; Ionizing radiation (IR); Tumor cell

Funding

  1. Shenzhen Science and Innovation Commission [KCXFZ202002011010232]
  2. Guangdong Basic and Applied Basic Research Foundation [2019A1515110069]
  3. Guangdong Nature Science Foundation [2016A030308007]
  4. National Natural Sciencec Foundation of China [NSFC 31900136]

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Radiotherapy is a common method for cancer treatment, but tumors may develop resistance to radiation due to the immune system. IFNgamma and CXCL10 play important roles in sensitizing tumor cells to ionizing radiation, and their interaction may contribute to effective killing of tumor cells in vitro.
Radiotherapy is a conventional approach for anti-cancer treatment, killing tumor cells through damaging cellular DNA. While increasing studies have demonstrated that tumors generated the tolerance to radiation and tumor immune system was found to be correlated to radiotherapy resistance. Therefore, it is critical to identify potential immune factors associated with the efficacy of radiotherapy. Here in this study, we evaluated the sensitivities of different tumor cells to radiation and determined HEp-2 cells as the radio-resistant tumor cells for further investigation. IFNgamma as a key regulator of host immune response showed the potential to sensitize tumors to ionizing radiation (IR). Besides, IFNgamma-induced CXC chemokine ligand 10 (CXCL10) was found to be necessary for effective IR-induced killing of cultured HEp-2 cells. Increased clonogenic survival was observed in CXCL10-depleted HEp-2 cells and CXCL10-KO cells. Additionally, the loss of CXCL10 in HEp-2 cells showed less progression of the G0/G1 phase to G2/M when exposed to IR (8 Gy). Local IR (20 Gy) to nude mice bearing HEp-2 tumors significantly reduced tumor burden, while fewer effects on tumor burden in mice carrying CXCL10-KO tumors were observed. We furtherly evaluated the possible roles the chemokine receptor CXCR3 plays in mediating the sensitivity of cultured HEp-2 cells to IR. Altered expression of CXCR3 in HEp-2 cells affected IRinduced killing of HEp-2 cells. Our data suggest the IFNgamma-activated CXCL10/CXCR3 axis may contribute to the effective radiation-induced killing of HEp-2 cells in vitro.

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