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Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:

2025 01

Page:

20-25

Research Field:

Publishing date:

Info

Title:

Mechanism of inhibiting the radiosensitization of IGF-1R on laryngeal carcinoma Hep-2 cells

Author(s):

ZHAO Ming¹; QIN Qiuzi²; HOU Xin³; YI Zhenying¹; ZHANG Beibei¹; GAO Ling¹

1.Department of Radiation Oncology£»2.Department of Imaging,Kaifeng Central Hospital£¬Henan Kaifeng 475000,China£»3.The First Affiliated Hospital of Henan University£¬Henan Kaifeng 475000,China.

Keywords:

laryngeal carcinoma; radiotherapy; IGF-1R; TKI; radiosensitivity

PACS:

R739.6

DOI:

10.3969/j.issn.1672-4992.2025.01.004

Abstract:

Objective:To explore the mechanism of tyrosine kinase inhibitor£¨TKI£©Linsitinib enhance the radiosensitivity in larngeal carcinoma cell line.Methods£ºWe examined the effect of Linsitinib on cell proliferation by MTT test.Then,the activation of AKT and ERK1/2 which were downstream of IGF-1R,were detected after X-ray irradiation(IR) and Linsitinib addition by Western blot.The cell cycle was examined by flow cytometry.The expression of Bax,Bcl-xl protein was assayed by Western blot.The survival fraction of Hep-2 was measured by clonogenic assay.Finally,Western blot analysis was performed to detect the expression level of DNA damage-related protein ¦Ã-H2AX.Results:Linsitinib,significantly suppressed Hep-2 cell proliferation.X-ray radiation can activate IGF-1R/AKT and IGF-1R/ERK signaling pathways,but both IGF-1R/AKT and IGF-1R/ERK signaling pathways were suppressed by Linsitinib£¬but Linsitinib combined with IR further inhibited the activation of IGF-1R/AKT and IGF-1R/ERK signaling pathways.Linsitinib induced Hep-2 cell cycle arrest in G2/M phase.Linsitinib combined with IR can increase the expression level of pro-apoptotic protein Bax and decrease the expression level of anti-apoptotic protein Bcl-xl.The results of cell cloning suggested that Linsitinib increased the radiosensitivity of IR cells.Western blot assay showed that Linsitinib increased the expression of ¦Ã-H2AX protein in X-ray irradiated cells.Conclusion:Linsitinib may increase the radiotherapy sensitivity of laryngeal cancer cells,and its mechanism may be related to inhibiting the activation of PI3K/AKT and Ras/MAPK cell proliferation signaling pathway,changing cell cycle,promoting cell apoptosis,and inducing genomic instability.

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