Arsenic trioxide induces autophagy and apoptosis in human glioma cells in vitro and in vivo through downregulation of survivin

Hui Wen Chiu, Yuan Soon Ho, Ying Jan Wang

研究成果: 雜誌貢獻文章同行評審

64 引文 斯高帕斯(Scopus)

摘要

Gliomas are the most aggressive of all human malignancies. Survivin is overexpressed in gliomas, and overexpression of survivin is associated with the progression of gliomas and the poor prognosis of glioma patients. Arsenic trioxide (ATO) is used in patients with acute promyelocytic leukemia and is active in vitro in several solid tumor cell lines. In the present study, the human glioma cell line U118-MG was used to investigate the anti-cancer effect of ATO in vitro and in vivo. The molecular mechanisms of the relationship between cell death (autophagy and apoptosis) and survivin were analyzed. ATO reduced cell viability through an increase in mitotic cells in a concentration-dependent manner. The mechanisms of ATO-induced autophagy and apoptosis were mediated by the inhibition of PI3K/Akt and the activation of MAPK signaling pathways. The ATO treatment of U118-MG cells pre-treated with specific chemical inhibitors of PI3K/AKT and MAPK significantly changed the cytotoxicity and the expression of survivin, suggesting that survivin plays a pivotal role in ATO-induced cell death. When U118-MG cells were transfected with survivin shRNA, the results demonstrated a significant increase in apoptotic and autophagic cells. In in vivo studies, the ATO treatment of SCID mice showed a significant tumor growth delay time and the decreased expression of survivin in tumor tissue. An important result from the current study is the finding that survivin could suppress both autophagy and apoptosis in glioma cells. This study suggests that ATO treatment or survivin inhibition could be a novel therapeutic strategy in malignant gliomas.

原文英語
頁(從 - 到)927-941
頁數15
期刊Journal of Molecular Medicine
89
發行號9
DOIs
出版狀態已發佈 - 九月 2011
對外發佈

ASJC Scopus subject areas

  • 分子醫學
  • 藥物發現
  • 遺傳學(臨床)

指紋

深入研究「Arsenic trioxide induces autophagy and apoptosis in human glioma cells in vitro and in vivo through downregulation of survivin」主題。共同形成了獨特的指紋。

引用此