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

Journal Article · Fri Jan 15 04:00:00 EST 2021 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2020.112382· OSTI ID:23195418

Lin, Yunting; Lu, Ruitao; Hou, Jingmei ^[1]; Fu, Wenmin ^[2]

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1. School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, 511436 (China)
2. Shenzhen International Institute for Biomedical Research, 1301 Guanguang Rd. 3F Building 1-B, Silver Star Hi-tech Park Longhua District, Shenzhen, Guangdong, 518116 (China)

Highlights: • IFNgamma/CXCL10/CXCR3 are necessary for effective IR-induced HEp-2 cell killing. • Local IR showed fewer effects on tumor burden in mice carrying CXCL10-KO xenografts. • Loss of CXCL10 showed blockage in the G0/G1 phase when exposed to a moderate dose of IR. 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 IR-induced 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.

• OSTI ID: 23195418
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 1 Vol. 398; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
CELL KILLING
DNA
IN VITRO
IONIZING RADIATIONS
LIGANDS
MICE
NEOPLASMS
RADIOSENSITIVITY
RADIOTHERAPY
RECEPTORS
TUMOR CELLS