Zhou Jie, Ye Wenjing, Guangming Yi, Jianming Huang, S. Deng, Minglun Li, Yimin Li, Yanqiong Song, Jiayu Zhang, Lichun Wei, S. Lu, Gui-Ming Zhu, J. Lang
{"title":"水杨酸通过激活AMPK/TSC2/mTOR通路抑制宫颈癌细胞生长并使其对放疗敏感","authors":"Zhou Jie, Ye Wenjing, Guangming Yi, Jianming Huang, S. Deng, Minglun Li, Yimin Li, Yanqiong Song, Jiayu Zhang, Lichun Wei, S. Lu, Gui-Ming Zhu, J. Lang","doi":"10.21203/rs.3.rs-960349/v1","DOIUrl":null,"url":null,"abstract":"\n Background\n\nRadioresistance remains a major clinical challenge in cervical cancer therapy. Salicylic acid (SA)-mediated direct activation of AMP–activated protein kinase (AMPK) is critical to radiosensitivity. However, limited data exists regarding the combination of SA and radiotherapy, even though there are several indications that this might be a promising treatment strategy. This study aimed to investigate the radiosensitizing effect of SA on human cervical cancer cells and its potential molecular mechanism.\nMethods\n\nCervical cancer cells were treated with SA and ionizing radiation. The expression of γ-H2AX was evaluated by immunofluorescence (IF) assay. Cell cycle and apoptosis were analyzed by flow cytometry. Western blot was performed to detect the protein level of AMPK/TSC2/mTOR pathway.\nResults\n\nSA inhibited basal proliferation of cervical cancer cells in a dose and time dependent manner. In addition, SA increased radiation-induced DNA damage, promoted apoptosis, triggered a redistribution of cell cycle from G2-M phase to G1-S phase of cervical cancer cells, and hence increased cell sensitivity to radiation. Moreover, SA treatment elevated the expression levels of p-AMPKα and p-TSC2, whereas the level of p-mTOR was significantly decreased.\nConclusion\n\nSA enhances the radiosensitivity of cervical cancer cells by targeting AMPK/TSC2/mTOR signaling pathway, and might serve as a promising therapeutic strategy to improve the efficacy of radiotherapy for cervical cancer.","PeriodicalId":34051,"journal":{"name":"Radiation Medicine and Protection","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2021-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Salicylic Acid Inhibits Growth and Sensitizes Cervical Cancer Cells to Radiotherapy by Activating AMPK/TSC2/mTOR Pathway\",\"authors\":\"Zhou Jie, Ye Wenjing, Guangming Yi, Jianming Huang, S. Deng, Minglun Li, Yimin Li, Yanqiong Song, Jiayu Zhang, Lichun Wei, S. Lu, Gui-Ming Zhu, J. Lang\",\"doi\":\"10.21203/rs.3.rs-960349/v1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"\\n Background\\n\\nRadioresistance remains a major clinical challenge in cervical cancer therapy. Salicylic acid (SA)-mediated direct activation of AMP–activated protein kinase (AMPK) is critical to radiosensitivity. However, limited data exists regarding the combination of SA and radiotherapy, even though there are several indications that this might be a promising treatment strategy. This study aimed to investigate the radiosensitizing effect of SA on human cervical cancer cells and its potential molecular mechanism.\\nMethods\\n\\nCervical cancer cells were treated with SA and ionizing radiation. The expression of γ-H2AX was evaluated by immunofluorescence (IF) assay. Cell cycle and apoptosis were analyzed by flow cytometry. Western blot was performed to detect the protein level of AMPK/TSC2/mTOR pathway.\\nResults\\n\\nSA inhibited basal proliferation of cervical cancer cells in a dose and time dependent manner. In addition, SA increased radiation-induced DNA damage, promoted apoptosis, triggered a redistribution of cell cycle from G2-M phase to G1-S phase of cervical cancer cells, and hence increased cell sensitivity to radiation. Moreover, SA treatment elevated the expression levels of p-AMPKα and p-TSC2, whereas the level of p-mTOR was significantly decreased.\\nConclusion\\n\\nSA enhances the radiosensitivity of cervical cancer cells by targeting AMPK/TSC2/mTOR signaling pathway, and might serve as a promising therapeutic strategy to improve the efficacy of radiotherapy for cervical cancer.\",\"PeriodicalId\":34051,\"journal\":{\"name\":\"Radiation Medicine and Protection\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2021-10-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Radiation Medicine and Protection\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.21203/rs.3.rs-960349/v1\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"Health Professions\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Radiation Medicine and Protection","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21203/rs.3.rs-960349/v1","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Health Professions","Score":null,"Total":0}
Salicylic Acid Inhibits Growth and Sensitizes Cervical Cancer Cells to Radiotherapy by Activating AMPK/TSC2/mTOR Pathway
Background
Radioresistance remains a major clinical challenge in cervical cancer therapy. Salicylic acid (SA)-mediated direct activation of AMP–activated protein kinase (AMPK) is critical to radiosensitivity. However, limited data exists regarding the combination of SA and radiotherapy, even though there are several indications that this might be a promising treatment strategy. This study aimed to investigate the radiosensitizing effect of SA on human cervical cancer cells and its potential molecular mechanism.
Methods
Cervical cancer cells were treated with SA and ionizing radiation. The expression of γ-H2AX was evaluated by immunofluorescence (IF) assay. Cell cycle and apoptosis were analyzed by flow cytometry. Western blot was performed to detect the protein level of AMPK/TSC2/mTOR pathway.
Results
SA inhibited basal proliferation of cervical cancer cells in a dose and time dependent manner. In addition, SA increased radiation-induced DNA damage, promoted apoptosis, triggered a redistribution of cell cycle from G2-M phase to G1-S phase of cervical cancer cells, and hence increased cell sensitivity to radiation. Moreover, SA treatment elevated the expression levels of p-AMPKα and p-TSC2, whereas the level of p-mTOR was significantly decreased.
Conclusion
SA enhances the radiosensitivity of cervical cancer cells by targeting AMPK/TSC2/mTOR signaling pathway, and might serve as a promising therapeutic strategy to improve the efficacy of radiotherapy for cervical cancer.