Mechanism by which dihydroartemisinin inhibits invasion and migration of glioma stem cells

doi:10.3969/j.issn.2095-4344.2016.06.001

Chinese Journal of Tissue Engineering Research ›› 2016, Vol. 20 ›› Issue (6): 765-770.doi: 10.3969/j.issn.2095-4344.2016.06.001

Mechanism by which dihydroartemisinin inhibits invasion and migration of glioma stem cells

Wu Yan-lin¹, Cai Zheng¹, Zhang Ming-zhi², Fu Xiao-rui²

¹Department of Oncology, Nanyang Centre Hospital, Nanyang 473000, Henan Province, China; ²Department of Oncology, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China

Received:2016-01-02 Online:2016-02-05 Published:2016-02-05
About author:Wu Yan-lin, Attending physician, Department of Oncology, Nanyang Centre Hospital, Nanyang 473000, Henan Province, China
Supported by:
the Major Scientific Funding Project of Henan Provincial Education Department, No. 13A320413

Abstract

Abstract:

BACKGROUND: Dihydroartmisinin can promote apoptosis of glioma cells GL261, but its effect on glioma stem cells is still unknown.

OBJECTIVE: To investigate the preliminary mechanism that dihydroartemisinin inhibits migration and invasion of glioma stem cells.

METHODS: Glioma stem cells were isolated from mouse malignant glioma cell lines GL261. Immunofluorescence analysis was conducted to identify the characteristics of glioma stem cells. Migration and invasion abilities of glioma stem cells were analyzed by Transwell assay. The mRNA expressions of Toll-like receptor 2, matrix metalloproteinase-2 and matrix metalloproteinase-9 were examined by real-time fluorescence quantitative PCR.

RESULTS AND CONCLUSION: The characteristics of glioma stem cells were identified by CD133 and Nestin staining. The migration and invasion of glioma stem cells were attenuated by dihydroartemisinin dose-dependently. Moreover, the mRNA expression of Toll-like receptor 2, matrix metalloproteinase-2 and matrix metalloproteinase-9 was also decreased by dihydroartemisinin in a dose dependent manner. These results suggest that dihydroartemisinin inhibits the migration and invasion of glioma stem cells probably through attenuation of Toll-like receptor signaling pathway.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Wu Yan-lin, Cai Zheng, Zhang Ming-zhi, Fu Xiao-rui. Mechanism by which dihydroartemisinin inhibits invasion and migration of glioma stem cells[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(6): 765-770.

Figures/Tables 3

References

[1] Hess KR, Broglio KR, Bondy ML. Adult glioma incidence trends in the United States, 1977-2000. Cancer. 2004;101(10):2293-2299.

[2] Rosenfeld MR, Pruitt AA. Management of malignant gliomas and primary CNS lymphoma: standard of care and future directions. Continuum (Minneap Minn). 2012;18(2):406-415.

[3] Bexell D, Svensson A, Bengzon J. Stem cell-based therapy for malignant glioma. Cancer Treat Rev. 2013; 39(4):358-365.

[4] Cheng L, Wu Q, Guryanova OA, et al. Elevated invasive potential of glioblastoma stem cells. Biochem Biophys Res Commun. 2011;406(4):643-648.

[5] Khoshnevisan A. An overview of therapeutic approaches to brain tumor stem cells. Med J Islam Repub Iran. 2012;26(1):31-40.

[6] 戴宜武,王振光,秦家振.脑胶质瘤治疗进展[J].中华临床医师杂志:电子版,2013,7(14):6225-6228.

[7] Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005; 352(10):987-996.

[8] 孙增峰,李文良,谷峰,等.胶质瘤耐药相关机制的研究进展[J].中华肿瘤防治杂志,2011,18(7):551-556.

[9] Van Meir EG, Hadjipanayis CG, Norden AD, et al. Exciting new advances in neuro-oncology: the avenue to a cure for malignant glioma. CA Cancer J Clin. 2010; 60(3):166-193.

[10] Singh SK, Hawkins C, Clarke ID, et al. Identification of human brain tumour initiating cells. Nature. 2004;432 (7015):396-401.

[11] 陈垒.MicroRNA-107在胶质瘤和胶质瘤干细胞中的生物学功能研究[D].广州:南方医科大学,2013.

[12] Singh SK, Clarke ID, Terasaki M, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res. 2003;63(18):5821-5828.

[13] 王凡.Toll样受体2在胶质瘤干细胞侵袭迁移中的作用及其机制探讨[D].重庆:第三军医大学,2012.

[14] Mao H, Gu H, Qu X, et al. Involvement of the mitochondrial pathway and Bim/Bcl-2 balance in dihydroartemisinin-induced apoptosis in human breast cancer in vitro. Int J Mol Med. 2013;31(1):213-218.

[15] Zhang JL, Wang Z, Hu W, et al. DHA regulates angiogenesis and improves the efficiency of CDDP for the treatment of lung carcinoma. Microvasc Res. 2013; 87:14-24.

[16] 尹怡,曹鎏,李飞,等.双氢青蒿素促进胶质瘤GL261细胞的凋亡[J].第三军医大学学报,2013,35(12):1179-1182.

[17] Davis TM, Binh TQ, Ilett KF, et al. Penetration of dihydroartemisinin into cerebrospinal fluid after administration of intravenous artesunate in severe falciparum malaria. Antimicrob Agents Chemother. 2003;47(1):368-370.
[18] Zhou HJ, Wang Z, Li A. Dihydroartemisinin induces apoptosis in human leukemia cells HL60 via downregulation of transferrin receptor expression. Anticancer Drugs. 2008;19(3):247-255.

[19] Chen J, McKay RM, Parada LF. Malignant glioma: lessons from genomics, mouse models, and stem cells. Cell. 2012;149(1):36-47.

[20] Jego G, Bataille R, Geffroy-Luseau A, et al. Pathogen-associated molecular patterns are growth and survival factors for human myeloma cells through Toll-like receptors. Leukemia. 2006;20(6):1130-1137.

[21] Szczepanski MJ, Czystowska M, Szajnik M, et al. Triggering of Toll-like receptor 4 expressed on human head and neck squamous cell carcinoma promotes tumor development and protects the tumor from immune attack.Cancer Res. 2009;69(7):3105-3113.

[22] Huang B, Zhao J, Li H, et al. Toll-like receptors on tumor cells facilitate evasion of immune surveillance. Cancer Res. 2005;65(12):5009-5014.

[23] Nair P, O'Donnell CM, Janasek K, et al. Lipopolysacchride-treated mammary carcinomas secrete proinflammatory chemokines and exhibit reduced growth rates in vivo, but not in vitro. Immunol Invest. 2009;38(8):730-748.

[24] Xie W, Huang Y, Xie W, et al. Bacteria peptidoglycan promoted breast cancer cell invasiveness and adhesiveness by targeting toll-like receptor 2 in the cancer cells. PLoS One. 2010;5(5):e10850.

[25] Watts C, West MA, Zaru R. TLR signalling regulated antigen presentation in dendritic cells. Curr Opin Immunol. 2010;22(1):124-130.

[26] Xie W, Wang Y, Huang Y, et al. Toll-like receptor 2 mediates invasion via activating NF-kappaB in MDA-MB-231 breast cancer cells. Biochem Biophys Res Commun. 2009;379(4):1027-1032.

[27] 董玮.基质金属蛋白酶2诱导大肠癌肿瘤细胞增殖与侵袭的试验研究[D]. 吉林:吉林大学,2012.

[28] Forsyth PA, Wong H, Laing TD, et al. Gelatinase-A (MMP-2), gelatinase-B (MMP-9) and membrane type matrix metalloproteinase-1 (MT1-MMP) are involved in different aspects of the pathophysiology of malignant gliomas. Br J Cancer. 1999;79(11-12):1828-1835.

[29] Van Meir EG, Hadjipanayis CG, Norden AD, et al. Exciting new advances in neuro-oncology: the avenue to a cure for malignant glioma. CA Cancer J Clin. 2010; 60(3):166-193.

[30] 程金湘.胶质瘤患者健康相关生命质量研究[D].西安:第四军医大学,2013.

Mechanism by which dihydroartemisinin inhibits invasion and migration of glioma stem cells

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