Borneol promotes apoptosis of Human Glioma Cells through regulating HIF-1a expression via mTORC1/eIF4E pathway

doi:10.7150/jca.45304

HFCAS OpenIR

	Borneol promotes apoptosis of Human Glioma Cells through regulating HIF-1a expression via mTORC1/eIF4E pathway
	Wang, Zeng 1,2,3; Li, Qinglin 1,2,3; Xia, Liang 2,3,4; Li, Xia 2,3,5; Sun, Caixing 1,2,3; Wang, Qiong 1,2,3; Cai, Xinjun 6; Yang, Guonong 1,2,3
	2020
发表期刊	JOURNAL OF CANCER
ISSN	1837-9664
通讯作者	Cai, Xinjun(zjtcmcxj@163.com) ; Yang, Guonong(yanggn@zjcc.org.cn)
摘要	The main reason for the failure of malignant glioma treatment is local tumor recurrence. Tumor cells in hypoxic microenvironment activate HIF-1 alpha transcription, and thus promoting tumor invasion and metastasis is one of the important reasons. In our previous study, we clearly established that borneol opens the blood-brain tumor barrier and its related mechanism. However, the effects of borneol itself on glioma proliferation have not yet been elucidated. Therefore, in this study, we evaluated the effect of borneol on glioma by constructing in vivo SD rat brain glioma model and in vitro human primary cultured glioma cell model. We found that borneol could suppress the proliferation of primary glioma cells and the tumor volume of SD rat brain glioma. Further, we measured the apoptosis effect induced by borneol in human primary cultured glioma cells. The results showed that the higher the concentration of borneol, the higher the apoptosis rate of human primary cultured glioma cells, but the effect was reversed after transfection of HIF-1 overexpression plasmid; In addition, borneol could downregulate the expression of Bcl-2 and upregulation the expression of Bax and caspase-3, similarly, the effect was also reversed after transfection of HIF-1 overexpression plasmid, suggesting that the apoptosis effect induced by borneol in human primary cultured glioma cells is mediated via HIF-1 alpha. Moreover, the bioinformatics analysis of correlation between HIF-1 alpha and apoptosis-related factors based on CGGA database showed that there was a positive correlation between the expression of eIF4E and HIF-1 alpha (P < 0.05), and in patients with high expression of eIF4E and HIF-1 alpha had poor survival and prognosis (P<0.001). It was further discovered that in the human primary cultured glioma cells borneol regulated HIF-1 alpha expression via mTORC1/eIF4E pathway. In conclusion, the findings of the present study suggest that HIF-1a may be a key factor in borneol induced apoptosis of glioma cells, and mTORC1 / eIF4E pathway is involved in the HIF-1 alpha regulation by borneol in malignant glioma. Our results not only reveal the target and molecular mechanism and action of borneol leading to promote apoptosis in glioma cells, but also provide experimental basis and theoretical support for the clinical application of borneol.
关键词	malignant glioma borneol HIF-1a apoptosis
DOI	10.7150/jca.45304
关键词[WOS]	HIF-1-ALPHA
收录类别	SCI
语种	英语
资助项目	1022 Talent Training Program of Zhejiang Cancer Hospital ; Zhejiang Provincial National Science Foundation of China[LQ18H290002] ; Zhejiang Provincial National Science Foundation of China[YY18H300008] ; Zhejiang Provincial National Science Foundation of China[LYQ20H280001] ; Zhejiang Medical and Health Science and Technology Project[2020364926] ; Zhejiang Medical and Health Science and Technology Project[2019RC127] ; Zhejiang Medical and Health Science and Technology Project[2018KY291] ; Zhejiang Medical and Health Science and Technology Project[2017KY260] ; Chinese medicine science and technology plan of Zhejiang Province[2016ZA039] ; National Science of Foundation of China[81502147]
项目资助者	1022 Talent Training Program of Zhejiang Cancer Hospital ; Zhejiang Provincial National Science Foundation of China ; Zhejiang Medical and Health Science and Technology Project ; Chinese medicine science and technology plan of Zhejiang Province ; National Science of Foundation of China
WOS研究方向	Oncology
WOS类目	Oncology
WOS记录号	WOS:000540767400019
出版者	IVYSPRING INT PUBL
引用统计	被引频次：12[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.hfcas.ac.cn:8080/handle/334002/102982
专题	中国科学院合肥物质科学研究院
通讯作者	Cai, Xinjun; Yang, Guonong
作者单位	1.Chinese Acad Sci, Inst Canc & Basic Med ICBM, Pharm Dept, Hangzhou 310022, Peoples R China 2.Univ Chinese Acad Sci, Canc Hosp, Hangzhou 310022, Peoples R China 3.Zhejiang Canc Hosp, Hangzhou 310022, Peoples R China 4.Chinese Acad Sci, Inst Canc & Basic Med ICBM, Neurotumor Surg Dept, Hangzhou 310022, Peoples R China 5.Chinese Acad Sci, Inst Canc & Basic Med ICBM, Canc Inst Dept, Hangzhou 310022, Peoples R China 6.ZheJiang Chinese Med & Western Med Integrated Hos, Dept Pharm, Hangzhou 310003, Zhejiang, Peoples R China
推荐引用方式 GB/T 7714	Wang, Zeng,Li, Qinglin,Xia, Liang,et al. Borneol promotes apoptosis of Human Glioma Cells through regulating HIF-1a expression via mTORC1/eIF4E pathway[J]. JOURNAL OF CANCER,2020,11.
APA	Wang, Zeng.,Li, Qinglin.,Xia, Liang.,Li, Xia.,Sun, Caixing.,...&Yang, Guonong.(2020).Borneol promotes apoptosis of Human Glioma Cells through regulating HIF-1a expression via mTORC1/eIF4E pathway.JOURNAL OF CANCER,11.
MLA	Wang, Zeng,et al."Borneol promotes apoptosis of Human Glioma Cells through regulating HIF-1a expression via mTORC1/eIF4E pathway".JOURNAL OF CANCER 11(2020).