Synergic antiproliferative and antiangiogenic effects of EGFR and mTor inhibitors on pancreatic cancer cells

Biochemical Pharmacology
Amalia AzzaritiAngelo Paradiso

Abstract

The in vitro efficacy of both EGFR inhibitor gefitinib and mTor inhibitor rapamycin, either administrated alone or in different combination schedules, was analysed in four pancreas cancer cell lines. Both drugs were found to induce cell growth inhibition, apoptosis as well as a slight but stable accumulation of cells in the G0/G1 phase. In all cell lines, neither gefitinib nor rapamycin affected EGFR and the expression of its downstream effectors. By contrast, gefitinib inhibited in a fast and completely way p-EGFR and partially p-Akt while a 3 days-rapamycin exposure resulted in the inhibition of the expression of both mTor and p70S6K. Moreover, after early stimulation, the mTor inhibitor produced a progressive, and almost complete inhibition of p-Akt. The analysis of combined gefitinib and rapamycin administration showed a clear schedule-dependent activity which turned out to be synergic only when gefitinib was given before rapamycin. This synergism seemed to depend on increase of both p-Akt and p70S6K inhibition, the greater the induction of apoptosis, the higher the decrease in cell cycle rate. Moreover, the antiangiogenic activity of the two drugs given in combination was demonstrated by a strong reduction of VEGF release ...Continue Reading

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References

May 9, 2001·The Journal of Surgical Research·S A ShahM P Callery
May 1, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Malcolm RansonEric K Rowinsky
Nov 8, 2002·Seminars in Oncology·Henry Q Xiong, James L Abbruzzese
Nov 26, 2002·The Journal of Biological Chemistry·Christopher J NelsenJeffrey H Albrecht
Jul 25, 2003·Cancer Biology & Therapy·Shile HuangPeter J Houghton
Aug 9, 2003·Biochemical Pharmacology·Jian-Ming XuAngelo Paradiso
Nov 26, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jeremy N RichHenry S Friedman
May 4, 2004·Nature Reviews. Cancer·Mary-Ann Bjornsti, Peter J Houghton
May 25, 2004·Molecular Pharmacology·Csilla Ozvegy-LaczkaBalázs Sarkadi
Aug 19, 2004·Cancer Chemotherapy and Pharmacology·Henry Q Xiong
Nov 17, 2004·British Journal of Cancer·G GiannelliA Paradiso
Dec 8, 2004·Current Cancer Drug Targets·Ravi D RaoJann N Sarkaria
Jan 1, 2005·Current Opinion in Oncology·Eric K Rowinsky
Dec 27, 2005·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Roberto BiancoGiampaolo Tortora
Jan 10, 2006·Seminars in Oncology·Hedy Lee Kindler
Jan 19, 2006·Therapeutic Drug Monitoring·Louis Y LeungJames J Zimmerman
Feb 3, 2006·Cancer Research·Kathryn E O'ReillyNeal Rosen
Feb 10, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·David A ReardonJeremy N Rich

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Citations

Jun 6, 2009·Cancer Chemotherapy and Pharmacology·Amalia AzzaritiAngelo Paradiso
Jun 10, 2009·Nature Reviews. Gastroenterology & Hepatology·Han H Wong, Nicholas R Lemoine
Feb 10, 2011·Annals of Oncology : Official Journal of the European Society for Medical Oncology·H Calvert, A Azzariti
Apr 22, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Lucy F ChenJennifer R Grandis
Jun 6, 2009·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Ryan J O DowlingNahum Sonenberg
Jan 5, 2013·Biochimica Et Biophysica Acta·S E KorsseW van Veelen
Jun 15, 2010·Pharmacology & Therapeutics·Michele VisentinGiuseppe Toffoli
Feb 18, 2010·Surgical Oncology Clinics of North America·Philip A Philip
Apr 28, 2009·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Paul DentSteven Grant
Mar 6, 2009·Current Opinion in Cell Biology·Pazit Polak, Michael N Hall
Nov 26, 2010·The Mount Sinai Journal of Medicine, New York·Soley Bayraktar, Caio M Rocha-Lima
Jan 11, 2013·Journal of Cellular and Molecular Medicine·Murielle Mimeault, Surinder K Batra
May 12, 2009·Biochemical Pharmacology·Silvia La MonicaPier Giorgio Petronini
Sep 20, 2011·European Journal of Pharmacology·Amalia AzzaritiAngelo Paradiso
Sep 30, 2010·International Journal of Obesity : Journal of the International Association for the Study of Obesity·C CataniaD Cota
Aug 5, 2010·British Journal of Cancer·K SchmidW Sieghart
Mar 1, 2008·Expert Review of Endocrinology & Metabolism·Kathrin ZitzmannChristoph J Auernhammer
Oct 16, 2009·Expert Review of Anticancer Therapy·R Pamela Mackenzie, A David McCollum
Aug 22, 2009·Expert Opinion on Therapeutic Targets·Xuerong Wang, Shi-Yong Sun
Nov 8, 2020·Cancer Chemotherapy and Pharmacology·Haeseong ParkAndrea Wang-Gillam
Jul 28, 2010·Applied Immunohistochemistry & Molecular Morphology : AIMM·Andrew M BellizziWendy L Frankel
Mar 5, 2009·Cellular Signalling·Vladimir RatushnyJoshua S Silverman

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