MiR-34a reverses radiation resistance on ECA-109 cells by inhibiting PI3K/AKT/mTOR signal pathway through downregulating the expression of SIRT1
| Autor: | Lei Wang, Fujun Hu, Zhenfu Fu, Fangzheng Wang, Tieming Xie, Fengqin Yan, Jun Fang, Zhimin Ye, Zhun Wang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_treatment
Down-Regulation Apoptosis Radiation Tolerance Esophageal squamous cell carcinoma Signal pathway 030218 nuclear medicine & medical imaging Phosphatidylinositol 3-Kinases 03 medical and health sciences 0302 clinical medicine Sirtuin 1 Cell Line Tumor Humans Effective treatment Medicine Radiology Nuclear Medicine and imaging neoplasms Protein kinase B PI3K/AKT/mTOR pathway Radiation resistance Cell Proliferation Radiological and Ultrasound Technology business.industry TOR Serine-Threonine Kinases digestive system diseases Radiation therapy MicroRNAs 030220 oncology & carcinogenesis Cancer research Esophageal Squamous Cell Carcinoma business Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | International Journal of Radiation Biology. 97:452-463 |
| ISSN: | 1362-3095 0955-3002 |
| Popis: | Radiotherapy is an effective treatment for esophageal squamous cell carcinoma (ESCC). However, many ESCC patients relapsed after receiving radiotherapy due to the inherent resistance. The function of miR-34a and SIRT1, as well as the correlation between miR-34a and SIRT1 has been widely claimed in multiple types of malignant tumors. This study aimed to investigate the effects of miR-34a on radiation resistance against ESCC and the underlying mechanism.In this study, CCK8, flow cytometry, wounding healing assays, and cell clone formation assay were used to determine the in vitro anti-tumor effects of radiation on radiation-resistant ESCC cell line (rECA-109). The luciferase activity and Western Blot assays were used to investigate the relationship among miR-34a, SIRT1, and the anti-radiation resistant effects. The xenograft experiments were used to verify the important function of miR-34a and SIRT1 in radiation resistance against ESCC. The apoptosis state of tumor tissues was evaluated by TUNEL assay.The introduction of miR-34a significantly induced the cell death and apoptosis of rECA-109 and inhibit the migration of rECA-109 treated by radiation. The anti-tumor effect was accompanied by the downregulation of SIRT1 and the inhibition of PI3K/AKT/mTOR signal pathway. The radiation resistance on rECA-109 cells was reversed by silencing SIRT1, accompanied by the PI3K/AKT/mTOR signal pathway inhibited. In vivo experiments revealed that the radiation resistance on ESCC was reversed by the introduction of miR-34a, the effect of which was promoted by the activation of SIRT1.Our results showed that miR-34a could reverse the radiation resistance on rECA-109 cells by downregulating the expression of SIRT1through inhibiting the PI3K-AKT-mTOR signal pathway. |
| Databáze: | OpenAIRE |
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