Sphingosine 1-phosphate antagonizes the effect of all-trans retinoic acid (ATRA) in a human colon cancer cell line by modulation of RAR尾 expression

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• 作者：De-Fu Sun^a ; ^b ; ¹ ; Zu-Hua Gao^c ; ¹ ; Hui-Ping Liu^a ; Yi Yuan^a ; Xian-Jun Qu^a ; ^{qxj@sdu.edu.cn}
• 关键词：Sphingosine 1-phosphate (S1P) ; Retinoids ; All-trans retinoic acid (ATRA) ; HT-29 cells ; Retinoid acid receptor 尾 (RAR尾) ; SphK2
• 刊名：Cancer Letters
• 出版年：2012
• 期刊代码：44_03043835
• 类别：med
• 出版时间：28 June, 2012
• 卷：319
• 期：2
• 页码：182-189
• 文件大小：610 K

摘要

All-trans retinoic acid (ATRA) is a promising therapeutic agent, but exhibits low efficacy against human cancers. We investigated the effect of sphingosine-1-phosphate (S1P) on ATRA activity in human colon cancer HT-29 cells. S1P antagonized ATRA activity on HT-29 cell proliferation and retinoic acid receptor beta (RAR尾) expression. S1P treatment or transient co-transfection with SphK2 expression vector antagonized ATRA-induced RAR尾 promoter activity. Proteasome inhibition prevented S1P-induced modulation of ATRA activity. Overall, S1P antagonized ATRA鈥檚 inhibitory effects by down-regulating RAR尾 expression, likely via the proteasome-dependent pathway. Decreasing S1P production or inhibiting SphK2 activity could enhance the efficacy of retinoids in cancer treatments.