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β-榄香烯下调缺氧诱导因子-1α及下游葡萄糖转运蛋白1基因增强肺腺癌移植瘤放射敏感性

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.

作者信息

Wu Wenbo, Hu Zhonghui, Zhao Qingtao, Zhang Xiaopeng, Zhang Hua, Wang Huien, Xue Wenfei, Yu Lei, Duan Guochen

机构信息

Department of Thoracic Surgery, Hebei General Hospital, Shijiazhuang, People's Republic of China.

Graduate School of Hebei North University, Zhangjiakou, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Nov 13;13:11627-11635. doi: 10.2147/OTT.S275956. eCollection 2020.

DOI:10.2147/OTT.S275956
PMID:33223837
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7671467/
Abstract

PURPOSE

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 () and glucose transporter protein-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 and was detected by real-time PCR, Western blotting and immunohistochemistry. The relationship between the radiosensitivity of β-elemene and the expression of and 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 and 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 and expression, suggesting that β-elemene may directly or indirectly inhibit the expression of and . There is a positive significant correlation between expression of and . and downstream could be used as a new target for the radiosensitization of NSCLC.

摘要

目的

研究β-榄香烯对A549细胞异种移植瘤放射敏感性的影响及其调控缺氧诱导因子-1α（HIF-1α）和葡萄糖转运蛋白-1（GLUT-1）表达的潜在机制。

方法

利用雄性裸鼠建立A549细胞移植瘤模型，研究β-榄香烯对非小细胞肺癌（NSCLC）放射敏感性的影响。采用实时荧光定量PCR、蛋白质免疫印迹法和免疫组织化学法检测HIF-1α和GLUT-1的表达。分析β-榄香烯的放射增敏作用与HIF-1α和GLUT-1表达之间的关系。

结果

β-榄香烯和放射治疗均不同程度地干预了移植瘤的生长。计算出增敏因子（EF=2.44>1）；45mg/kg的β-榄香烯对放射敏感性的增强作用最显著。β-榄香烯与放射联合应用时，HIF-1α和GLUT-1的表达明显降低，且二者基因之间呈正相关。

结论

β-榄香烯对A549细胞异种移植瘤具有放射增敏作用。其潜在的分子机制可能与下调HIF-1α和GLUT-1的表达有关，提示β-榄香烯可能直接或间接抑制HIF-1α和GLUT-1的表达。HIF-1α和GLUT-1的表达之间存在显著正相关。HIF-1α及其下游分子可作为NSCLC放射增敏治疗的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bd1/7671467/626be7b7e945/OTT-13-11627-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bd1/7671467/b845f86e79dd/OTT-13-11627-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bd1/7671467/9514cc13d95a/OTT-13-11627-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bd1/7671467/254f29cd4598/OTT-13-11627-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bd1/7671467/626be7b7e945/OTT-13-11627-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bd1/7671467/b845f86e79dd/OTT-13-11627-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bd1/7671467/9514cc13d95a/OTT-13-11627-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bd1/7671467/254f29cd4598/OTT-13-11627-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bd1/7671467/626be7b7e945/OTT-13-11627-g0004.jpg

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