OncoTargets and Therapy (Nov 2020)
Down-Regulation of Hypoxia-Inducible Factor-1α and Downstream Glucose Transporter Protein-1 Gene by β-elemene Enhancing the Radiosensitivity of Lung Adenocarcinoma Transplanted Tumor
Abstract
Wenbo Wu,1,2,* Zhonghui Hu,1,3,* Qingtao Zhao,1,* Xiaopeng Zhang,1 Hua Zhang,1 Huien Wang,1 Wenfei Xue,1 Lei Yu,1 Guochen Duan4 1Department of Thoracic Surgery, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 2Graduate School of Hebei North University, Zhangjiakou, People’s Republic of China; 3Graduate School of Hebei Medical University, Shijiazhuang, People’s Republic of China; 4Department of Thoracic Surgery, Hebei Children’s Hospital, Shijiazhuang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guochen DuanDepartment of Thoracic Surgery, Hebei Children’s Hospital, No. 133, Jianhua Main Street South, Yuhua District, Shijiazhuang 050000, People’s Republic of ChinaTel +86 13513380703Email [email protected]: To study the effect of β-elemene on the radiosensitivity of A549 cell xenograft tumor and potential mechanisms by which β-elemene regulates the expression of hypoxia-inducible factor-1α (HIF-1α) and glucose transporter protein-1 (GLUT-1).Methods: Using an A549 cell transplantation tumor model with male nude mice, we studied the effect of β-elemene on the radiosensitivity of non-small cell lung cancer (NSCLC). The expression of HIF-1α and GLUT-1 was detected by real-time PCR, Western blotting and immunohistochemistry. The relationship between the radiosensitivity of β-elemene and the expression of HIF-1α and GLUT-1 was analyzed.Results: β-elemene and radiotherapy intervened in the growth of transplanted tumors in varying degrees. The enhancement factor (EF=2.44> 1) was calculated; β-elemene at 45 mg/kg had the most significant enhanced effect on radiosensitivity. When β-elemene was used in combination with radiation, the expression of HIF-1α and GLUT-1 was significantly decreased, and there was a positive correlation between the two genes.Conclusion: β-elemene exhibits a radiosensitizing effect on A549 cell xenograft tumor. The underlying molecular mechanism is probably associated with the down-regulation of HIF-1α and GLUT-1 expression, suggesting that β-elemene may directly or indirectly inhibit the expression of HIF-1α and GLUT-1. There is a positive significant correlation between expression of HIF-1α and GLUT-1. HIF-1α and downstream GLUT-1 could be used as a new target for the radiosensitization of NSCLC.Keywords: β-elemene, radiosensitivity, transplanted tumor, HIF-1α, GLUT-1
