Dataset Information

Simultaneous Inhibition of EGFR and HER2 via Afatinib Augments the Radiosensitivity of Nasopharyngeal Carcinoma Cells.

ABSTRACT: Ionizing radiation (IR) is the central component of the therapeutic scheme for nasopharyngeal carcinoma (NPC) at present. Previous studies show that inhibition of epidermal growth factor receptor (EGFR) enhances the radiosensitivity of NPC; however the effects of EGFR-targeted agents are limited. In this study, we observed that simultaneously inhibition of EGFR and HER2 by afatinib could augment the radiosensitivity of NPC cells; this approach has an advantage over erlotinib-mediated inhibition of EGFR alone. The afatinib-induced augmentation of NPC cell radiosensitivity was associated with increases in apoptosis and accumulation of DNA damage that were induced by radiation. In addition, the crosstalk between radiation-induced activities and EGFR-, and HER2-related downstream pathways may contribute to the enhancement of radiosensitivity. Our findings indicate the potential of repositioning afatinib or other ERBB-family-targeted agents for improving radiation response in NPC cells.

SUBMITTER: Huang F

PROVIDER: S-EPMC6548161 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Simultaneous Inhibition of EGFR and HER2 via Afatinib Augments the Radiosensitivity of Nasopharyngeal Carcinoma Cells.

Huang Fangling F Liang Xujun X Min Xiaoli X Zhang Ye Y Wang Guoqiang G Peng Zhengrong Z Peng Fang F Li Maoyu M Chen Lin L Chen Yongheng Y

Journal of Cancer 20190512 9

Ionizing radiation (IR) is the central component of the therapeutic scheme for nasopharyngeal carcinoma (NPC) at present. Previous studies show that inhibition of epidermal growth factor receptor (EGFR) enhances the radiosensitivity of NPC; however the effects of EGFR-targeted agents are limited. In this study, we observed that simultaneously inhibition of EGFR and HER2 by afatinib could augment the radiosensitivity of NPC cells; this approach has an advantage over erlotinib-mediated inhibition ...[more]

PMID: 31205567

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Project description:Radioresistance prevails as one of the largest obstacles in the clinical treatment of nasopharyngeal carcinoma (NPC). Meanwhile, tumor-derived extracellular vesicles (TEVs) possess the ability to manipulate radioresistance in NPC. However, its mechanism remains to be further explored. Therefore, the current study set out to explore the mechanism of microRNA (miR)-142-5p delivered by TEVs in regard to the radiosensitivity of NPC. Firstly, peripheral blood samples were collected from patients with radioresistance and radiosensitivity, followed by RT-qPCR detection of miR-142-5p expression. A dual-luciferase reporter assay was carried out to elucidate the targeting relationship of miR-142-5p with HGF and EGF. In addition, radiotherapy-resistant NPC cell models were established by screening NPC cells with gradient increasing radiation exposure, and co-incubated with EVs isolated from miR-142-5p mimic-transfected NPC cells, followed by overexpression of HGF and EGF. Moreover, cell viability was detected by means of MTS, cell proliferation with a colony formation assay, cell apoptosis with flow cytometry, and expression patterns of related genes with the help of Western blot analysis. NPC xenotransplantation models in nude mice were also established by subcutaneous injection of 5-8FR cells to determine apoptosis, tumorigenicity, and radiosensitivity in nude mice. It was found that miR-142-5p was poorly expressed in peripheral blood from NPC patients with radioresistance. Mechanistic experimentation illustrated that miR-142-5p inversely targeted HGF and EGF to inactivate the HGF/c-Met and EGF/EGFR pathways, respectively. NPC cell apoptosis was observed to be augmented, while their radioresistance and proliferation were restricted by EVs-miR-142-5p or HGF silencing, or EGF silencing. Furthermore, EVs-miR-142-5p inhibited growth and radioresistance and accelerated the apoptosis of radiotherapy-resistant NPC cells in nude mice by inhibiting the HGF/c-Met and EGF/EGFR pathways. Collectively, our findings indicated that TEVs might inhibit the HGF/c-Met and EGF/EGFR pathways by delivering miR-142-5p into radiotherapy-resistant NPC cells to enhance radiosensitivity in NPC.

Dataset Information

Simultaneous Inhibition of EGFR and HER2 via Afatinib Augments the Radiosensitivity of Nasopharyngeal Carcinoma Cells.

Publications

Simultaneous Inhibition of EGFR and HER2 via Afatinib Augments the Radiosensitivity of Nasopharyngeal Carcinoma Cells.

Similar Datasets

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