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Ramucirumab and GSK1838705A Enhance the Inhibitory Effects of Low Concentration Sorafenib and Regorafenib Combination on HCC Cell Growth and Motility
- Source :
- Cancers, Vol 11, Iss 6, p 787 (2019), Cancers, Volume 11, Issue 6
- Publication Year :
- 2019
- Publisher :
- MDPI AG, 2019.
-
Abstract
- Several new multikinase inhibitors have recently been introduced into clinical practice for hepatocellular carcinoma (HCC) therapy. Small increases in survival were reported as well as considerable toxicity. There is thus a need for effective therapies with lower toxicities. We examined whether a combination of sorafenib and regorafenib might also be effective at very low concentrations, with resulting potential for lessened clinical toxicity. MTT test, clonogenic assay, Ki67 staining and cell cycle analysis were assessed for cell proliferation and Annexin V and western blotting analysis relative to the expression of cleaved Caspase-3 and BID for cell apoptosis. In these experimental conditions cell growth and migration were potently inhibited and apoptosis induced even in HCC cells producing high alpha fetoprotein (AFP) levels (clinically worse prognosis). The combination also inhibited levels of the two HCC biomarkers, AFP and des gamma carboxy prothrombin (DCP). Additional inhibition of Vascular Endothelial Growth Factor Receptor (VEGFR) or Insulin-like Growth Factor 1 Receptor (IGF1R) enhanced effects on AFP and DCP levels, cell growth inhibition and MAPK and PI3K/Akt signaling inhibition due to sorafenib/regorafenib combination. These combinations have the potential for decreased toxicity while simultaneously enhancing therapeutic effects. This potential decrease in toxicity is being explored in ongoing studies.
- Subjects :
- 0301 basic medicine
Sorafenib
MAPK/ERK pathway
Cancer Research
α fetoprotein
medicine.medical_treatment
lcsh:RC254-282
Article
combination therapy
03 medical and health sciences
chemistry.chemical_compound
des-γ-carboxyprothrombin
0302 clinical medicine
multi-kinase inhibitors
Regorafenib
synergism
medicine
Clonogenic assay
Insulin-like growth factor 1 receptor
Chemistry
Cell growth
Growth factor
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
digestive system diseases
3. Good health
030104 developmental biology
Oncology
insulin-like growth factor 1 receptor
030220 oncology & carcinogenesis
Toxicity
Cancer research
medicine.drug
vascular endothelial growth factor receptor
Subjects
Details
- Language :
- English
- ISSN :
- 20726694
- Volume :
- 11
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Cancers
- Accession number :
- edsair.doi.dedup.....cbc5694c53008befd6af2d254843573a