细胞凋亡.pdf

Clinical
Cancer
1 Cancer Therapy: Preclinical Research
2 Q1 Phenylarsine Oxide Induces Apoptosis in Bax- and
3 Bak-Deficient Cells Through Upregulation of Bim
4
5 AU Biyun Ni1,2,QiMa1,2, Baowei Li1,2, Lixia Zhao1,2, Yong Liu1,2, Yushan Zhu3, and Quan Chen1,3
6 Abstract
7 Purpose: Bax and Bak are regarded as key mediators for cytochrome c (Cyt c) release and apoptosis. Loss
8 of Bax or Bak is often reported in human cancers and renders resistance of these cancerous cells to
9 chemotherapy. Here, we investigated that phenylarsine oxide (PAO) could induce Bax/Bak-independent
10 apoptosis.
11 Experimental Design: Annexin V/propidium iodide (PI) staining, terminal deoxynucleotidyl transfer-
12 ase–mediated dUTP nick end labeling (TUNEL) staining, and caspase activation assays were conducted to
À À
13 detect apoptosis in Bax/Bak-deficient mouse embryonic fibroblasts (MEF) and HCT116 bax / colorectal
14 cancer cells. Cyt c release and Bim expression were assessed by Western blotting and immunostaining. Bim
15 was stably knocked down by short hairpin RNA. Immunoprecipitation was applied to detect the interaction
16 between Bim and Bcl-2. Both subcutaneous and colorectal orthotopic tumor implantation models were
17 used in nude mice to investigate the effect of PAO in vivo.
18 Results: PAO triggered Cyt c release and apoptosis in a Bax/Bak-independent manner. Bim and Bcl-2
19 the expression o