期刊
INTERNATIONAL JOURNAL OF CANCER
卷 125, 期 10, 页码 2323-2331出版社
WILEY
DOI: 10.1002/ijc.24573
关键词
pancreatic cancer; drug resistance; cancer stem cell; cell surface marker; ATP-binding cassette transporter
类别
资金
- Republic of Korea [0720390]
- National R&D Program for Cancer Control\
- Ministry for Health. Welfare and Family affairs
- Brain Korea 21 Project for Medical Sciences of Yonsei University College of Medicine
Accumulating evidence suggests that tumors are composed of a heterogeneous cell population with a small subset of cancer stem cell (CSCs) that sustain tumor formation and growth. Recently. there have been efforts to explain drug resistance of cancer cells based on the concept of CSCs having an intrinsic defoxifying mechanism. In the present study, to investigate the role of CSCs in acquiring chemoresistance in pancreatic cancer, gemcitabine-resistant cells were established by exposure to serially escalated doses of gemcitabine in HPAC and CFPAC-I cells. Gemcitabine-resistant cells were more tumorigenic in vitro and in vivo, and had greater sphere-forming activily than parental cells. After high(lose gemcitabine treatment to eliminate most of the cells, CD44(+) cells proliferated and reconstituted the population of resistant cells. CD44(+)CD24(+)ESA(+) cells aimedas a small subset in the resistant cell population. Among ATP-binding cassette (ABC) transporters, which are known as file mechanism of drug resistance in CSCs, ABCB1 (MDR1) was significantly augmented during the acquisition of drug resistance. ABC transporter inhibitor veraparmil resensitized the resistant cells to gemcitabine in Close-dependent manner and RNA interference of CD44 inhibited the clonogenic activity of resistant cells. In human pancreatic cancer samples, CD44 expression was correlated with histologic grade and the patients with CD44-positive tumors showed poor prognosis. These data indicate that cancer stern-like cells were expanded during the acquisition of gemcitabine resistance and in therapeutic application, targeted therapy against file CD44 or ABC transporter inhibitors could be applied to overcome drug resistance in the treatment of pancreatic cancer. (C) 2009 UICC
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据