Merck
  • 主页
  • 查找结果
  • Chronic chemotherapeutic stress promotes evolution of stemness and WNT/beta-catenin signaling in colorectal cancer cells: implications for clinical use of WNT-signaling inhibitors.

Chronic chemotherapeutic stress promotes evolution of stemness and WNT/beta-catenin signaling in colorectal cancer cells: implications for clinical use of WNT-signaling inhibitors.

Oncotarget (2015-06-05)
Meriam Ayadi, Anaïs Bouygues, Djamila Ouaret, Nathalie Ferrand, Salem Chouaib, Jean-Paul Thiery, Christian Muchardt, Michèle Sabbah, Annette K Larsen
摘要

Most solid tumors contain a subfraction of cells with stem/progenitor cell features. Stem cells are naturally chemoresistant suggesting that chronic chemotherapeutic stress may select for cells with increased "stemness". We carried out a comprehensive molecular and functional analysis of six independently selected colorectal cancer (CRC) cell lines with acquired resistance to three different chemotherapeutic agents derived from two distinct parental cell lines. Chronic drug exposure resulted in complex alterations of stem cell markers that could be classified into three categories: 1) one cell line, HT-29/5-FU, showed increased "stemness" and WNT-signaling, 2) three cell lines showed decreased expression of stem cell markers, decreased aldehyde dehydrogenase activity, attenuated WNT-signaling and lost the capacity to form colonospheres and 3) two cell lines displayed prominent expression of ABC transporters with a heterogeneous response for stem cell markers. While WNT-signaling could be attenuated in the HT-29/5-FU cells by the WNT-signaling inhibitors ICG-001 and PKF-118, this was not accompanied by any selective growth inhibitory effect suggesting that the cytotoxic activity of these compounds is not directly linked to WNT-signaling inhibition. We conclude that classical WNT-signaling inhibitors have toxic off-target activities that need to be addressed for clinical development.

材料
货号
品牌
产品描述

Sigma-Aldrich
十二烷基硫酸钠, BioReagent, suitable for electrophoresis, for molecular biology, ≥98.5% (GC)
Sigma-Aldrich
氯化钠, BioXtra, ≥99.5% (AT)
Sigma-Aldrich
十二烷基硫酸钠, ReagentPlus®, ≥98.5% (GC)
Sigma-Aldrich
十二烷基硫酸钠, ACS reagent, ≥99.0%
Sigma-Aldrich
氯化钠, for molecular biology, DNase, RNase, and protease, none detected, ≥99% (titration)
Sigma-Aldrich
DAPI, for nucleic acid staining
Sigma-Aldrich
乙二胺四乙酸, ACS reagent, 99.4-100.6%, powder
Sigma-Aldrich
氯化钠 溶液, 5 M in H2O, BioReagent, for molecular biology, suitable for cell culture
Sigma-Aldrich
十二烷基硫酸钠 溶液, BioUltra, for molecular biology, 10% in H2O
Sigma-Aldrich
氯化钠, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for plant cell culture, ≥99%
Sigma-Aldrich
苯甲磺酰氟, ≥98.5% (GC)
Sigma-Aldrich
氯化钠 溶液, 0.9% in water, BioXtra, suitable for cell culture
SAFC
氯化钠 溶液, 5 M
Sigma-Aldrich
十二烷基硫酸钠, ≥99.0% (GC), dust-free pellets
Sigma-Aldrich
氯化钠 溶液, 5 M
Sigma-Aldrich
十二烷基硫酸钠, BioUltra, for molecular biology, ≥99.0% (GC)
Sigma-Aldrich
乙二胺四乙酸, BioUltra, anhydrous, ≥99% (titration)
Sigma-Aldrich
氯化钠, meets analytical specification of Ph. Eur., BP, USP, 99.0-100.5%
Sigma-Aldrich
十二烷基硫酸钠, 92.5-100.5% based on total alkyl sulfate content basis
Sigma-Aldrich
乙二胺四乙酸 溶液, 0.02% in DPBS (0.5 mM), sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
十二烷基硫酸钠, BioXtra, ≥99.0% (GC)
Sigma-Aldrich
十二烷基硫酸钠 溶液, BioUltra, for molecular biology, 20% in H2O
Sigma-Aldrich
乙二胺四乙酸, anhydrous, crystalline, BioReagent, suitable for cell culture
Sigma-Aldrich
氯化钠, BioUltra, for molecular biology, ≥99.5% (AT)
Sigma-Aldrich
乙二胺四乙酸, purified grade, ≥98.5%, powder
Sigma-Aldrich
苯乙酸, 99%
Sigma-Aldrich
苯甲磺酰氟, ≥99.0% (T)
Supelco
十二烷基硫酸钠, dust-free pellets, suitable for electrophoresis, for molecular biology, ≥99.0% (GC)
Sigma-Aldrich
氯化钠 溶液, 0.85%
Sigma-Aldrich
氯化钠 溶液, BioUltra, for molecular biology, ~5 M in H2O