Autophagic cell death induced by 5-FU in Bax or PUMA deficient human colon cancer cell

被引：69

作者：

Xiong, Hai-yan ^{[1
]}

Guo, Xian-ling ^{[1
]}

Bu, Xin-xin ^{[1
]}

Zhang, Shan-shan ^{[1
]}

Ma, Nan-nan ^{[1
]}

Song, Jian-rui ^{[1
]}

Hu, Fei ^{[1
]}

Tao, Shuang-fen ^{[1
]}

Sun, Kai ^{[1
]}

Li, Rong ^{[1
]}

Wu, Meng-chao ^{[1
]}

Wei, Li-xin ^{[1
]}

机构：

[1] Second Mil Med Univ, Tumor Immunol & Gene Therapy Ctr, Eastern Hepatobiliary Surg Hosp, Shanghai 200438, Peoples R China

来源：

CANCER LETTERS | 2010年 / 288卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Autophagic cell death; Apoptosis; Bax; PUMA; mTOR; MALIGNANT GLIOMA-CELLS; MAMMALIAN TARGET; TUMOR-SUPPRESSOR; KINASE-B; APOPTOSIS; INHIBITION; PROTEIN; DISEASE; MACROAUTOPHAGY; CHEMOTHERAPY;

D O I：

10.1016/j.canlet.2009.06.039

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Autophagy is a membrane process that results in the transporting of cellular contents to lysosomes for degradation. Autophagic cell death is another way of programed cell death called type If PCD, which has complicated connection with apoptosis, both of these two types of cell death play an important role in tumor development. In this study, we investigated chemotherapeutic agent induced cell death pathway in wild type (WT), Bax(-/-) and PUMA(-/-) HCT116 cells. Bax or PUMA deficient cells had similar chemosensitivity to VV7 cells but were defective in undergoing apoptosis. The results of electron microscopy and GFP-LC3 localization assay showed that autophagy was induced in Bax or PUMA deficient cells but not in WT cells. mTOR activity was decreased in Bax or PUMA deficient cells which further indicated the up-regulation of autophagy. Inhibition of autophagy by 3-Methyladenine (3-MA) decreased the cell death in Bax or PUMA deficient cells. Taken together, these results suggest that autophagic cell death can be used as an alternative cell death pathway in apoptosis defective cells and may bring a new target for cancer therapy. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

引用

页码：68 / 74

页数：7

共 35 条

[1] The tumor suppressor PTEN positively regulates macroautophagy by inhibiting the phosphatidylinositol 3-kinase/protein kinase B pathway [J].