Back to Search
Start Over
Reversibility of regorafenib effects in hepatocellular carcinoma cells
- Source :
- Cancer Chemotherapy and Pharmacology. 72:869-877
- Publication Year :
- 2013
- Publisher :
- Springer Science and Business Media LLC, 2013.
-
Abstract
- 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.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.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.Removal of regorafenib from growth-inhibited cells resulted in a JNK-dependent recovery of growth and migration.
- Subjects :
- Drug
Cancer Research
medicine.medical_specialty
Carcinoma, Hepatocellular
MAP Kinase Signaling System
Pyridines
media_common.quotation_subject
Blotting, Western
Antineoplastic Agents
Biology
Toxicology
Article
chemistry.chemical_compound
Drug withdrawal
Cell Movement
Cell Line, Tumor
Internal medicine
Regorafenib
medicine
Humans
Potency
Neoplasm Invasiveness
Pharmacology (medical)
Doxorubicin
Cell Proliferation
media_common
Pharmacology
Cell growth
Kinase
Phenylurea Compounds
Liver Neoplasms
Hep G2 Cells
Vitamin K 1
medicine.disease
Endocrinology
Oncology
chemistry
Hepatocellular carcinoma
Cancer research
medicine.drug
Subjects
Details
- ISSN :
- 14320843 and 03445704
- Volume :
- 72
- Database :
- OpenAIRE
- Journal :
- Cancer Chemotherapy and Pharmacology
- Accession number :
- edsair.doi.dedup.....79e4ffe7abdfc9960ee5cc3c0517b8a5