Abstract

Purpose Multikinase growth inhibitors inhibit their target kinases with varying potency. Patients often require lower doses or therapy breaks due to drug toxicities. To evaluate the effects of drug withdrawal on hepatocellular carcinoma cells after incubation with growth-inhibitory concentrations of regorafenib, cell growth, migration and invasion, and signaling were examined. Methods Cell proliferation, motility, and invasion were analyzed by MTT, wound healing, and invasion assays, respectively, and MAPK pathway protein markers were analyzed by Western blot. Results After regorafenib removal, cell growth, migration, and invasion recovered. Repeated drug exposure resulted in changes in cell growth patterns. Recovery could be blocked by sub-growth-inhibitory concentrations of either doxorubicin or vitamin K1. Recovery of growth was associated with increased phospho-JNK, phospho-p38, and phospho-STAT3 levels. The recovery of growth, migration, and signaling were blocked by a JNK inhibitor. Conclusions Removal of regorafenib from growth-inhibited cells resulted in a JNK-dependent recovery of growth and migration. Loading... Cancer Chemotherapy and PharmacologyCancer Chemotherapy and Pharmacology Look Inside Within this Article Introduction Materials and methods Results Discussion Conclusions References References Other actions Export citation Register for Journal Updates About This Journal Reprints and Permissions Add to Papers Share Share this content on Facebook Share this content on Twitter Share this content on LinkedIn

Autore Pugliese

• Resta Leonardo

Tutti gli autori

• RESTA L.

Titolo volume/Rivista

Non Disponibile

Anno di pubblicazione

2013

ISSN

0344-5704

ISBN

Non Disponibile

Numero di citazioni Wos

9

Ultimo Aggiornamento Citazioni

Non Disponibile

Numero di citazioni Scopus

9

Ultimo Aggiornamento Citazioni

Non Disponibile

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile