机构：[1]Departments of Otorhinolaryngology, The First Affiliated Hospital, Nanjing Medical University, Nanjing外科系统耳鼻咽喉科江苏省人民医院[2]Departments of Dermatology, The First Affiliated Hospital, Nanjing Medical University, Nanjing江苏省人民医院[3]Department of Dermatology, The First Affiliated Hospital of Kunming Medical University, Kunming内科科室皮肤科昆明医科大学附属第一医院[4]Key Laboratory of Reproductive Medicine, School of Public Health, Nanjing Medical University, Nanjing[5]Laboratory of Reproductive Medicine, Research Center for Bone and Stem Cells, Nanjing Medical University, Nanjing[6]Department of Dermatology, BenQ Medical Center, Nanjing Medical University, Nanjing, China
Recent published studies suggest that increasing levels of ceramides enhance the chemo-sensitivity of curcumin. Using in vitro approaches, we analyzed the impact of sphingosine kinase-1 (SphK-1) inhibition on ceramide production, and evaluated SphK1 inhibitor II (SKI-II) as a potential curcumin chemo-sensitizer in ovarian cancer cells. We found that SphK1 is overexpressed in ovarian cancer patients' tumor tissues and in cultured ovarian cancer cell lines. Inhibition of SphK1 by SKI-II or by RNA interference (RNAi) knockdown dramatically enhanced curcumin-induced apoptosis and growth inhibition in ovarian cancer cells. SKI-II facilitated curcumin-induced ceramide production, p38 activation and Akt inhibition. Inhibition of p38 by the pharmacological inhibitor (SB 203580), a dominant-negative expression vector, or by RNAi diminished curcumin and SKI-II co-administration-induced ovarian cancer cell apoptosis. In addition, restoring Akt activation introducing a constitutively active Akt, or inhibiting ceramide production by fumonisin B1 also inhibited the curcumin plus SKI-II co-administration-induced in vitro anti-ovarian cancer effect, suggesting that ceramide accumulation, p38 activation and Akt inhibition are downstream effectors. Our findings suggest that low, well-tolerated doses of SKI-II may offer significant improvement to the clinical curcumin treatment of ovarian cancer. (Cancer Sci 2012; 103: 15381545)
基金：
National Natural Science FoundationNational Natural Science Foundation of China [810701297, 81101188, 30671894, 30972822, 30801016]; Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD); Health Promotion Project of Jiangsu Province [XK200719, XK200731, RC2007065, RC2011071]; Science & Technology Development Foundation of Nanjing Medical University, the People's Republic of China [2010NJMUZ19]
第一作者机构：[1]Departments of Otorhinolaryngology, The First Affiliated Hospital, Nanjing Medical University, Nanjing
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通讯作者：
推荐引用方式(GB/T 7714)：
Yang Yan-li,Ji Chao,Cheng Lei,et al.Sphingosine kinase-1 inhibition sensitizes curcumin-induced growth inhibition and apoptosis in ovarian cancer cells[J].CANCER SCIENCE.2012,103(8):1538-1545.doi:10.1111/j.1349-7006.2012.02335.x.
APA：
Yang, Yan-li,Ji, Chao,Cheng, Lei,He, Li,Lu, Chun-cheng...&Bi, Zhi-gang.(2012).Sphingosine kinase-1 inhibition sensitizes curcumin-induced growth inhibition and apoptosis in ovarian cancer cells.CANCER SCIENCE,103,(8)
MLA：
Yang, Yan-li,et al."Sphingosine kinase-1 inhibition sensitizes curcumin-induced growth inhibition and apoptosis in ovarian cancer cells".CANCER SCIENCE 103..8(2012):1538-1545
医学