Modulation of Regorafenib effects on HCC cell lines by epidermal growth factor

Rosalba D'Alessandro, Maria Grazia Refolo, Catia Lippolis, Nicola Carella, Caterina Messa, Aldo Cavallini, Brian Irving Carr

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Purpose: Blood platelet numbers are correlated to growth and aggressiveness of several tumor types, including hepatocellular carcinoma (HCC). We previously found that platelet lysates (hPLs) also stimulated growth and migration, and antagonized the growth-inhibitory and apoptotic effects of both Sorafenib and Regorafenib, two multikinase inhibitors, on three HCC cell lines. In this study, in vitro function of human epidermal growth factor (EGF) with and without Sorafenib or Regorafenib was investigated. Methods: An ELISA kit was used to evaluate the EGF concentrations in hPLs. In vitro function of EGF was assessed with proliferation MTT test. Apoptosis assay, scratch assays, and Transwell assays were performed for apoptosis, invasion, and migration, respectively. MAPK Activation Kit was used to explore MAPK phosphorylation. Results: EGF antagonized the growth inhibition of Regorafenib on three HCC cell lines. Regorafenib-mediated growth inhibition was blocked by 70 % when the cells were pre-treated with EGF. EGF also blocked Regorafenib-induced apoptosis, as well as Regorafenib-induced decreases in cell migration and invasion. The EGF effects were in turn antagonized by concomitant addition to the cultures of EGF receptor antagonist Erlotinib, showing that the EGF receptor was involved in the mechanisms of EGF-mediated blocking of Regorafenib effects. Erlotinib also partially blocked the effects of hPLs in antagonizing Regorafenib-mediated growth inhibition, showing that EGF was an important component of hPL actions. Conclusions: All these results show that EGF antagonized Regorafenib-mediated growth and migration inhibition and apoptosis induction in HCC cells and reinforce the idea that microenvironment can influence cancer drug actions.

Original languageEnglish
Pages (from-to)1237-1245
Number of pages9
JournalCancer Chemotherapy and Pharmacology
Volume75
Issue number6
DOIs
Publication statusPublished - Apr 24 2015

Fingerprint

Epidermal Growth Factor
Hepatocellular Carcinoma
Cells
Modulation
Cell Line
Growth
Apoptosis
Assays
Platelets
Epidermal Growth Factor Receptor
regorafenib
Phosphorylation
Platelet Count
Cell Movement
Tumors
Neoplasms
Blood
Blood Platelets
Chemical activation
Enzyme-Linked Immunosorbent Assay

Keywords

  • Epidermal growth factor
  • HCC cells
  • Platelets
  • Regorafenib

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Toxicology

Cite this

Modulation of Regorafenib effects on HCC cell lines by epidermal growth factor. / D'Alessandro, Rosalba; Refolo, Maria Grazia; Lippolis, Catia; Carella, Nicola; Messa, Caterina; Cavallini, Aldo; Carr, Brian Irving.

In: Cancer Chemotherapy and Pharmacology, Vol. 75, No. 6, 24.04.2015, p. 1237-1245.

Research output: Contribution to journalArticle

D'Alessandro, Rosalba ; Refolo, Maria Grazia ; Lippolis, Catia ; Carella, Nicola ; Messa, Caterina ; Cavallini, Aldo ; Carr, Brian Irving. / Modulation of Regorafenib effects on HCC cell lines by epidermal growth factor. In: Cancer Chemotherapy and Pharmacology. 2015 ; Vol. 75, No. 6. pp. 1237-1245.
@article{7fd275fa6d9646cbb6eb329a061de136,
title = "Modulation of Regorafenib effects on HCC cell lines by epidermal growth factor",
abstract = "Purpose: Blood platelet numbers are correlated to growth and aggressiveness of several tumor types, including hepatocellular carcinoma (HCC). We previously found that platelet lysates (hPLs) also stimulated growth and migration, and antagonized the growth-inhibitory and apoptotic effects of both Sorafenib and Regorafenib, two multikinase inhibitors, on three HCC cell lines. In this study, in vitro function of human epidermal growth factor (EGF) with and without Sorafenib or Regorafenib was investigated. Methods: An ELISA kit was used to evaluate the EGF concentrations in hPLs. In vitro function of EGF was assessed with proliferation MTT test. Apoptosis assay, scratch assays, and Transwell assays were performed for apoptosis, invasion, and migration, respectively. MAPK Activation Kit was used to explore MAPK phosphorylation. Results: EGF antagonized the growth inhibition of Regorafenib on three HCC cell lines. Regorafenib-mediated growth inhibition was blocked by 70 {\%} when the cells were pre-treated with EGF. EGF also blocked Regorafenib-induced apoptosis, as well as Regorafenib-induced decreases in cell migration and invasion. The EGF effects were in turn antagonized by concomitant addition to the cultures of EGF receptor antagonist Erlotinib, showing that the EGF receptor was involved in the mechanisms of EGF-mediated blocking of Regorafenib effects. Erlotinib also partially blocked the effects of hPLs in antagonizing Regorafenib-mediated growth inhibition, showing that EGF was an important component of hPL actions. Conclusions: All these results show that EGF antagonized Regorafenib-mediated growth and migration inhibition and apoptosis induction in HCC cells and reinforce the idea that microenvironment can influence cancer drug actions.",
keywords = "Epidermal growth factor, HCC cells, Platelets, Regorafenib",
author = "Rosalba D'Alessandro and Refolo, {Maria Grazia} and Catia Lippolis and Nicola Carella and Caterina Messa and Aldo Cavallini and Carr, {Brian Irving}",
year = "2015",
month = "4",
day = "24",
doi = "10.1007/s00280-015-2751-6",
language = "English",
volume = "75",
pages = "1237--1245",
journal = "Cancer Chemotherapy and Pharmacology",
issn = "0344-5704",
publisher = "Springer Verlag",
number = "6",

}

TY - JOUR

T1 - Modulation of Regorafenib effects on HCC cell lines by epidermal growth factor

AU - D'Alessandro, Rosalba

AU - Refolo, Maria Grazia

AU - Lippolis, Catia

AU - Carella, Nicola

AU - Messa, Caterina

AU - Cavallini, Aldo

AU - Carr, Brian Irving

PY - 2015/4/24

Y1 - 2015/4/24

N2 - Purpose: Blood platelet numbers are correlated to growth and aggressiveness of several tumor types, including hepatocellular carcinoma (HCC). We previously found that platelet lysates (hPLs) also stimulated growth and migration, and antagonized the growth-inhibitory and apoptotic effects of both Sorafenib and Regorafenib, two multikinase inhibitors, on three HCC cell lines. In this study, in vitro function of human epidermal growth factor (EGF) with and without Sorafenib or Regorafenib was investigated. Methods: An ELISA kit was used to evaluate the EGF concentrations in hPLs. In vitro function of EGF was assessed with proliferation MTT test. Apoptosis assay, scratch assays, and Transwell assays were performed for apoptosis, invasion, and migration, respectively. MAPK Activation Kit was used to explore MAPK phosphorylation. Results: EGF antagonized the growth inhibition of Regorafenib on three HCC cell lines. Regorafenib-mediated growth inhibition was blocked by 70 % when the cells were pre-treated with EGF. EGF also blocked Regorafenib-induced apoptosis, as well as Regorafenib-induced decreases in cell migration and invasion. The EGF effects were in turn antagonized by concomitant addition to the cultures of EGF receptor antagonist Erlotinib, showing that the EGF receptor was involved in the mechanisms of EGF-mediated blocking of Regorafenib effects. Erlotinib also partially blocked the effects of hPLs in antagonizing Regorafenib-mediated growth inhibition, showing that EGF was an important component of hPL actions. Conclusions: All these results show that EGF antagonized Regorafenib-mediated growth and migration inhibition and apoptosis induction in HCC cells and reinforce the idea that microenvironment can influence cancer drug actions.

AB - Purpose: Blood platelet numbers are correlated to growth and aggressiveness of several tumor types, including hepatocellular carcinoma (HCC). We previously found that platelet lysates (hPLs) also stimulated growth and migration, and antagonized the growth-inhibitory and apoptotic effects of both Sorafenib and Regorafenib, two multikinase inhibitors, on three HCC cell lines. In this study, in vitro function of human epidermal growth factor (EGF) with and without Sorafenib or Regorafenib was investigated. Methods: An ELISA kit was used to evaluate the EGF concentrations in hPLs. In vitro function of EGF was assessed with proliferation MTT test. Apoptosis assay, scratch assays, and Transwell assays were performed for apoptosis, invasion, and migration, respectively. MAPK Activation Kit was used to explore MAPK phosphorylation. Results: EGF antagonized the growth inhibition of Regorafenib on three HCC cell lines. Regorafenib-mediated growth inhibition was blocked by 70 % when the cells were pre-treated with EGF. EGF also blocked Regorafenib-induced apoptosis, as well as Regorafenib-induced decreases in cell migration and invasion. The EGF effects were in turn antagonized by concomitant addition to the cultures of EGF receptor antagonist Erlotinib, showing that the EGF receptor was involved in the mechanisms of EGF-mediated blocking of Regorafenib effects. Erlotinib also partially blocked the effects of hPLs in antagonizing Regorafenib-mediated growth inhibition, showing that EGF was an important component of hPL actions. Conclusions: All these results show that EGF antagonized Regorafenib-mediated growth and migration inhibition and apoptosis induction in HCC cells and reinforce the idea that microenvironment can influence cancer drug actions.

KW - Epidermal growth factor

KW - HCC cells

KW - Platelets

KW - Regorafenib

UR - http://www.scopus.com/inward/record.url?scp=84929966274&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929966274&partnerID=8YFLogxK

U2 - 10.1007/s00280-015-2751-6

DO - 10.1007/s00280-015-2751-6

M3 - Article

C2 - 25907508

AN - SCOPUS:84929966274

VL - 75

SP - 1237

EP - 1245

JO - Cancer Chemotherapy and Pharmacology

JF - Cancer Chemotherapy and Pharmacology

SN - 0344-5704

IS - 6

ER -