MHY1485 enhances X-irradiation-induced apoptosis and senescence in tumor cells
| العنوان: | MHY1485 enhances X-irradiation-induced apoptosis and senescence in tumor cells |
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| المؤلفون: | Yu Sogo, Lue Sun, Kumi Morikawa, Yuki Sugiura |
| المصدر: | Journal of Radiation Research |
| بيانات النشر: | Oxford University Press (OUP), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Senescence, senescence, Morpholines, Health, Toxicology and Mutagenesis, Apoptosis, medicine.disease_cause, Carcinoma, Lewis Lung, Mice, 03 medical and health sciences, 0302 clinical medicine, Cell Line, Tumor, medicine, Animals, Radiology, Nuclear Medicine and imaging, Fundamental Radiation Science, Radiosensitivity, Cellular Senescence, Tumor Stem Cell Assay, PI3K/AKT/mTOR pathway, Radiation, Triazines, Chemistry, TOR Serine-Threonine Kinases, Endoplasmic reticulum, mammalian target of rapamycin (mTOR), Cell Cycle, Endoplasmic Reticulum Stress, Genes, p53, Mitochondria, Neoplasm Proteins, Genes, ras, 030104 developmental biology, Cell culture, 030220 oncology & carcinogenesis, Colonic Neoplasms, Cancer research, Unfolded protein response, AcademicSubjects/SCI00960, MHY1485, AcademicSubjects/MED00870, Lipid Peroxidation, Drug Screening Assays, Antitumor, Oxidative stress, Signal Transduction |
| الوصف: | The mammalian target of rapamycin (mTOR) is a sensor of nutrient status and plays an important role in cell growth and metabolism. Although inhibition of mTOR signaling promotes tumor cell death and several mTOR inhibitors have been used clinically, recent reports have shown that co-treatment with MHY1485, an mTOR activator, enhances the anti-cancer effects of anti-PD-1 antibody and 5-fluorouracil. However, it remains unclear whether MHY1485 treatment alters the effects of radiation on tumor cells. In this study, the radiosensitizing effects of MHY1485 were investigated using murine CT26 and LLC cell lines. We examined mTOR signaling, tumor cell growth, colony formation, apoptosis, senescence, oxidative stress, p21 accumulation and endoplasmic reticulum (ER) stress levels in cells treated with MHY1485 and radiation, either alone or together. We found that MHY1485 treatment inhibited growth and colony formation in both cell lines under irradiation and no-irradiation conditions, results that were not fully consistent with MHY1485’s known role in activating mTOR signaling. Furthermore, we found that combined treatment with MHY1485 and radiation significantly increased apoptosis and senescence in tumor cells in association with oxidative stress, ER stress and p21 stabilization, compared to radiation treatment alone. Our results suggested that MHY1485 enhances the radiosensitivity of tumor cells by a mechanism that may differ from MHY1485’s role in mTOR activation. |
| تدمد: | 1349-9157 0449-3060 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::96d9fb71f10d7fcd49dc94d4e158f3adTest https://doi.org/10.1093/jrr/rrab057Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....96d9fb71f10d7fcd49dc94d4e158f3ad |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13499157 04493060 |
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