Akt inhibitor SC66 promotes cell sensitivity to cisplatin in chemoresistant ovarian cancer cells through inhibition of COL11A1 expression

doi:10.1038/s41419-019-1555-8

Chia Nan University of Pharmacy & Science Institutional Repository > 藥理學院 > 化妝品應用與管理系(所) > 期刊論文 > Item 310902800/32686

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標題:	Akt inhibitor SC66 promotes cell sensitivity to cisplatin in chemoresistant ovarian cancer cells through inhibition of COL11A1 expression
作者:	Wu, Yi-Hui Huang, Yu-Fang Chien-Chin Chen(陳建欽) Chou, Cheng-Yang
貢獻者:	Natl Cheng Kung Univ, Coll Med, Natl Cheng Kung Univ Hosp, Dept Obstet & Gynecol Chia Yi Christian Hosp, Depardnent Pathol Chia Nan Univ Pharm & Sci, Dept Cosmet Sci
關鍵字:	PLECKSTRIN HOMOLOGY DOMAIN PROGNOSTIC-SIGNIFICANCE PI3K/AKT PATHWAY ACTIVATION BREAST GENE PIK3CA TWIST PROTEIN IDENTIFICATION
日期:	2019-04
上傳時間:	2020-07-29 13:55:16 (UTC+8)
出版者:	NATURE PUBLISHING GROUP
摘要:	We studied Akt inhibition using SC66 in a NOD-SCID xenograft mouse model and a panel of eight ovarian cancer cell lines. Elevated phospho-Akt levels in cancerous tissue were associated with short progression-free survival and overall survival. Cell sensitivity to SC66 was inversely correlated with phospho-Akt and COL11A1 expression levels, as well as resistance to cisplatin or paclitaxel. SC66 inhibited phosphorylation of Akt and its downstream effectors 4EBP1 and p70S6 kinase. SC66 also attenuated expression of TWIST1 and Mcl-1, factors important in cell invasiveness and antiapoptosis, respectively. SC66-sensitized chemoresistant cells to cisplatin and paclitaxel treatment, and promoted apoptosis. In addition, SC66 inhibited COL11A1 expression via decreased binding of CCAAT/enhancer-binding protein beta (c/EBP beta), reducing chemoresistance and decreasing binding of nuclear transcription factor Y (NF-YA) to COL11A1. A mouse xenograft experiment demonstrated that SC66 treatment caused a reduction in tumor formation and enhanced the therapeutic efficacy of cisplatin. This study demonstrates the role of Akt in ovarian tumor progression and chemoresistance, and supports the application of SC66 as a therapy for ovarian cancer.
關聯:	Cell Death & Disease, v.10, 322
显示于类别:	[化妝品應用與管理系(所)] 期刊論文

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