Increased expression of telomere-related proteins correlates with resistance to radiation in human laryngeal cancer cell lines

Tang, Tian; Zhou, Fen; Han, Lihua; Yu, Haijun; Xie, Conghua; Zhou, Yifei; Liu, Shiquan

doi:10.3892/or_00000381

Cited by 13 publications

(1 citation statement)

References 22 publications

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“…In our previous study, we found that GLUT-1 is expressed at high levels in a Hep-2 laryngeal cancer cell line expressing high levels of CD133 (CD133 + -Hep-2),26 and GLUT-1 siRNA improved the radiosensitivity of CD133 + -Hep-2 cells. There have been other studies on radioresistant Hep-2 (Hep-2R) 27,28. However, the correlation between high-level GLUT-1 expression and radioresistance in Hep-2R cells expressing high levels of CD133 (CD133 + -Hep-2R) has not been previously reported.…”

Section: Introductionmentioning

confidence: 99%

<p>GLUT-1 siRNA Enhances Radiosensitization Of Laryngeal Cancer Stem Cells Via Enhanced DNA Damage, Cell Cycle Redistribution, And Promotion Of Apoptosis In Vitro And In Vivo</p>

Zhong¹,

Qi²,

Zhou³

et al. 2019

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BackgroundRadiotherapy does not show good efficacy against laryngeal cancer due to radioresistance. Cancer stem cells (CSCs) are considered among the causes of radioresistance. Inhibition of glucose transporter-1 (GLUT-1) using GLUT-1 small interfering RNA (siRNA) may enhance the radiosensitivity of laryngeal cancer cells, but the underlying cellular mechanisms remain unclear.MethodsThe CD133+-Hep-2R cell line was established with repeated irradiation and magnetic-activated cell sorting. The effects of irradiation on CD133+-Hep-2R cells were examined by CCK-8 assay, Transwell assay, quantitative real-time polymerase chain reaction (RT-PCR), and Western blotting. The effects of GLUT-1 siRNA on the radiosensitivity of CD133+-Hep-2/2R cells were examined by RT-PCR, Western blotting, CCK-8 assay, colony formation assay, and Transwell assay in vitro and in a xenograft tumor model in nude mice. The cellular mechanism of enhanced radiosensitivity associated with GLUT-1 siRNA was investigated. The cell cycle and apoptosis rate were analyzed by flow cytometry, and the repair capability was examined by determining the levels of RAD51 and DNA-PKcs.ResultsCD133+-Hep-2/2R cells showed stronger proliferation, lower apoptosis rate, lower percentage of G0/G1 phase cells, higher percentages of S and G2/M phase cells, and higher expression levels of GLUT-1 than Hep-2/2R cells. Transfection with GLUT-1 siRNA inhibited the proliferation and invasive capability of CD133+-Hep-2R cells by inhibiting GLUT-1 expression, which also caused a redistribution of the cell cycle (higher proportion of cells in the G0/G1 phase and lower proportion in the S and G2/M phases), increased the apoptosis rate, and reduced DNA repair capability by suppressing RAD51 and DNA-PKcs expression.ConclusionThe results of this study suggest that GLUT-1 siRNA can enhance the radiosensitivity of CD133+-Hep-2R cells by inducing a redistribution of cell cycle phases, inhibiting DNA repair capability, and increasing apoptosis. Inhibition of GLUT-1 may have therapeutic potential for interventions to increase the radiosensitivity of laryngeal CSCs.

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Section: Introductionmentioning

confidence: 99%

<p>GLUT-1 siRNA Enhances Radiosensitization Of Laryngeal Cancer Stem Cells Via Enhanced DNA Damage, Cell Cycle Redistribution, And Promotion Of Apoptosis In Vitro And In Vivo</p>

Zhong¹,

Qi²,

Zhou³

et al. 2019

OTT

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Novel combination of tanshinone I and lenalidomide induces chemo-sensitivity in myeloma cells by modulating telomerase activity and expression of shelterin complex and its associated molecules

et al. 2018

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Telomere Profiling: Toward Glioblastoma Personalized Medicine

et al. 2012

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Despite a standard of care combining surgery, radiotherapy (RT), and temozolomide chemotherapy, the average overall survival (OS) of glioblastoma patients is only 15 months, and even far lower when the patient cannot benefit from this combination. Therefore, there is a strong need for new treatments, such as new irradiation techniques. Against this background, carbon ion hadrontherapy, a new kind of irradiation, leads to a greater biological response of the tumor, while minimizing adverse effects on healthy tissues in comparison with RT. As carbon ion hadrontherapy is restricted to RT-resistant patients, photon irradiation resistance biomarkers are needed. Long telomeres and high telomerase activity have been widely associated with photon radioresistance in other cancers. Moreover, telomere protection, telomere function, and telomere length (TL) also depend on the shelterin protein complex (TRF1, TRF2, TPP1, POT1, TIN2, and hRAP1). We thus decided to evaluate an enlarged telomeric status (TL, telomerase catalytic subunit, and the shelterin component expression level) as a potential radioresistance biomarker in vitro using cellular models and ex vivo using patient tumor biopsies. In addition, nothing was known about the role of telomeres in carbon ion response. We thus evaluated telomeric status after both types of irradiation. We report here a significant correlation between TL and the basal POT1 expression level and photon radioresistance, in vitro, and a significant increase in the OS of patients with long telomeres or a high POT1 level, in vivo. POT1 expression was predictive of patient response irrespective of the TL. Strikingly, these correlations were lost, in vitro, when considering carbon irradiation. We thus propose (1) a model of the implications of telomeric damage in the cell response to both types of irradiation and (2) assessment of the POT1 expression level and TL using patient tumor biopsies to identify radioresistant patients who could benefit from carbon hadrontherapy.

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Increased expression of telomere-related proteins correlates with resistance to radiation in human laryngeal cancer cell lines

Cited by 13 publications

References 22 publications

<p>GLUT-1 siRNA Enhances Radiosensitization Of Laryngeal Cancer Stem Cells Via Enhanced DNA Damage, Cell Cycle Redistribution, And Promotion Of Apoptosis In Vitro And In Vivo</p>

<p>GLUT-1 siRNA Enhances Radiosensitization Of Laryngeal Cancer Stem Cells Via Enhanced DNA Damage, Cell Cycle Redistribution, And Promotion Of Apoptosis In Vitro And In Vivo</p>

Novel combination of tanshinone I and lenalidomide induces chemo-sensitivity in myeloma cells by modulating telomerase activity and expression of shelterin complex and its associated molecules

Telomere Profiling: Toward Glioblastoma Personalized Medicine

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