Oxaliplatin enhances TRAIL-induced apoptosis in gastric cancer cells by CBL-regulated death receptor redistribution in lipid rafts

被引：95

作者：

Xu, Ling ^{[1
]}

Qu, Xiujuan ^{[1
]}

Zhang, Ye ^{[1
]}

Hu, Xuejun ^{[2
]}

Yang, Xianghong ^{[3
]}

Hou, Kezuo ^{[1
]}

Teng, Yuee ^{[1
]}

Zhang, Jingdong ^{[1
]}

Sada, Kiyonao ^{[4
]}

Liu, Yunpeng ^{[1
]}

机构：

[1] China Med Univ, Hosp 1, Dept Med Oncol, Shenyang 110001, Peoples R China

[2] China Med Univ, Hosp 1, Dept Resp Med, Shenyang 110001, Peoples R China

[3] China Med Univ, Shengjing Hosp, Dept Pathol, Shenyang 110004, Peoples R China

[4] Univ Fukui, Sch Med, Dept Pathol Sci, Div Microbiol, Fukui 9101193, Japan

来源：

FEBS LETTERS | 2009年 / 583卷 / 05期

关键词：

TRAIL; Oxaliplatin; Gastric cancer; Apoptosis; Lipid rafts; Cbl; ADVANCED ESOPHAGOGASTRIC CANCER; UP-REGULATION; CISPLATIN; LIGAND; CAPECITABINE; CHEMOTHERAPY; EXPRESSION; TUMORS; AKT;

D O I：

10.1016/j.febslet.2009.02.014

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor family that selectively induces apoptosis in cancer cells. However, gastric cancer cells are insensitive to TRAIL. In the present study, we show that oxaliplatin enhanced TRAIL-induced apoptosis of MGC803, BGC823, and SGC7901 cells. Oxaliplatin promoted death receptor 4 (DR4) and death receptor 5 (DR5) clustering into aggregated lipid rafts, while the cholesterol-sequestering agent nystatin partially prevented lipid raft aggregation, DR4 and DR5 clustering, and reduced apoptosis. Furthermore, the expression of the casitas B-lineage lymphoma (Cbl) family was downregulated by oxaliplatin. Transfection of c-Cbl or Cbl-b partially reversed oxaliplatin-induced lipid raft aggregation. These results indicated that oxaliplatin enhanced TRAIL-induced gastric cancer cell apoptosis at least partially through Cbl-regulated death receptor redistribution in lipid rafts. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：943 / 948

页数：6

共 23 条

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