Abstract
Background
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.
Methods
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.
Results
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.
Conclusion
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.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Additional information
Funding
Notes on contributors
Zhimin Ye
Zhimin Ye, PhD, is a doctor-in-charge at the Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
Tieming Xie
Tieming Xie, BS, is a doctor-in-charge at the Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
Fengqin Yan
Fengqin Yan, PhD, is an associate chief physician at the Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
Lei Wang
Lei Wang, BS, is a doctor-in-charge at the Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
Jun Fang
Jun Fang, MS, is a doctor-in-charge at the Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
Zhun Wang
Zhun Wang, BS, is an associate chief physician at the Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
Fujun Hu
Fujun Hu, BS, is a chief physician at the Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
Fangzheng Wang
Fangzheng Wang, MS, is an associate chief physician at the Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
Zhenfu Fu
Zhenfu Fu, BS, is a chief physician at the Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, China.