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学科主题: 临床医学
题名:
beta-arrestin2 inhibits opioid-induced breast cancer cell death through Akt and caspase-8 pathways
作者: Zhao, M.1,2; Zhou, G.1; Zhang, Y.1; Chen, T.1,2; Sun, X.5; Stuart, C.2; Hanley, G.3; Li, J.1; Zhang, J.1; Yin, D.2,4
关键词: Breast cancer ; beta-arrestin ; opioid ; Akt ; caspase-8 ; cell death
刊名: NEOPLASMA
发表日期: 2009
卷: 56, 期:2, 页:108-113
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: BETA-ARRESTIN 2 ; MORPHINE ; APOPTOSIS ; PHOSPHORYLATION ; PROTEIN ; MICE
英文摘要:

beta-arrestins, a family of regulatory and scaffold proteins, are well-known negative regulators of G-protein-coupled receptors (GPCRs) including opioid receptors. Recent studies have shown that beta-arrestin2 plays a potential role in inhibiting cell death. It has been reported that opioids such as morphine induce cell death at high concentrations (>500 mu M for 24 hours), which is similar to morphine plasma concentrations in cancer patients receiving chronic morphine treatment for pain relievers. However, the role of beta-arrestin2 in opioid-induced cell death remains to be elucidated. We report here that beta-arrestin2 significantly blocks morphine-induced number of cell death in human breast cancer MCF-7 and MDA-MB231 cells. Suppression of endogenous beta-arrestin2 by specific RNA interfering (RNAi) and morphine treatment significantly attenuates the levels of phosphorylated Akt compared with inhibition of beta-arrestin2 or morphine treatment alone. However, blockade of morphine-induced cell death by beta-arrestin2 seems to be dependent on the inhibition of caspase-8, as inhibition of beta-arrestin2 and morphine treatment significantly enhanced the levels of cleaved caspase-8. These studies show for the first time that beta-arrestin2 blocks morphine-induced cell death through anti-apoptotic Akt and pro-apoptotic caspase-8 pathways. Therefore, targeting beta-arrcstin2 may be useful for treating side effects of opioids as pain relievers for cancer patients.

语种: 英语
所属项目编号: DA020120 ; ETSU RDC 0048 ; 07-026M
项目资助者: National Institutes of Health (NIH) ; East Tennessee State University Research Development Committee ; ETSU RDC
WOS记录号: WOS:000263775100004
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/59840
Appears in Collections:北京大学第二临床医学院_期刊论文

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作者单位: 1.Shandong Univ, Sch Med, Inst Pathol & Pathophysiol, Jinan 250012, Shandong, Peoples R China
2.E Tennessee State Univ, James Quillen Coll Med, Dept Internal Med, Johnson City, TN 37614 USA
3.E Tennessee State Univ, James Quillen Coll Med, Dept Lab Anim Resources, Johnson City, TN 37614 USA
4.E Tennessee State Univ, James Quillen Coll Med, Dept Pharmacol, Johnson City, TN 37614 USA
5.Peking Univ, Peoples Hosp, Dept Obstet & Gynecol, Beijing 100044, Peoples R China

Recommended Citation:
Zhao, M.,Zhou, G.,Zhang, Y.,et al. beta-arrestin2 inhibits opioid-induced breast cancer cell death through Akt and caspase-8 pathways[J]. NEOPLASMA,2009,56(2):108-113.
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