The Sequence-Dependent Cytotoxic Effect of Trastuzumab in Combination With 5-Fluorouracil or Cisplatin on Gastric Cancer Cell Lines

被引：5
|
作者：
Li, Xiao-Ling [1 ,2 ]
Yi, Shao-Qiong [3 ]
Xu, Jian-Ming [1 ]
Zhang, Yang [4 ]
Yingying-Feng [1 ]
Chen, Wei [3 ]
Song, San-Tai [1 ]
机构：
[1] Beijing 307 Hosp, Ctr Canc, Beijing 100071, Peoples R China
[2] Capital Med Univ, Dept Pharm, Xuanwu Hosp, Beijing, Peoples R China
[3] Beijing Inst Microbiol & Epidemiol, State Key Lab Pathogen & Biosecur, Beijing, Peoples R China
[4] Dalian Med Univ, Affiliated Hosp 2, Dalian, Peoples R China
来源：
CANCER INVESTIGATION | 2010年 / 28卷 / 10期
关键词：
Trastuzumab; 5-Fluorouracil; Cisplatin; Gastric cancer; HER-2/neu; RECEPTOR TYROSINE KINASE; PHASE-III TRIAL; LUNG-CANCER; HUMAN-BREAST; THYMIDYLATE SYNTHASE; MONOCLONAL-ANTIBODY; ANTITUMOR-ACTIVITY; GEFITINIB; GROWTH; CHEMOTHERAPY;
D O I：
10.3109/07357907.2010.483512
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
The effect of trastuzumab on patients with HER-2/neu (HER2)-positive gastric cancer has been confirmed in a phase III clinical trial (ToGA study). However, the optimized sequence and synergic mechanism of trastuzumab and chemotherapy are not clear. Our study investigated the effects and mechanisms of trastuzumab in combination with 5-Fluorouracil (5-Fu) or cisplatin (DDP) on gastric cancer cell lines. Flow cytometry was used to determine HER2 expression and cell cycle. MTT assay was performed to evaluate cytotoxicity. Western blotting and RT-PCR were used to analyze signaling transduction and mRNA expression. Sequential 5-Fu followed by trastuzumab and trastuzumab plus DDP followed by trastuzumab produced the best inhibitory effects. Inhibition of HER2-PI3K-AKT signal transduction, downregulation of nucleotide excision repair cross-complementation 1 (ERCC1), and interference with cell cycle distribution may elucidate the synergism between trastuzumab and chemotherapy. These results provide some evidence for designing a rational regime when trastuzumab is being considered to be used in patients with gastric cancer.
引用
收藏
页码：1038 / 1047
页数：10
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