Abstract
This work aimed to explore the induction of cetuximab-resistant human nasopharyngeal carcinoma (hNPC) 5-8F/Erbitux cells and the mechanisms of drug resistance. The 5-8F cells with high EGFR expression and cetuximab sensitivity were screened and then induced by stepwise exposure to increasing doses of cetuximab. Western blot was conducted to detect protein levels. Our results are as follows: we successfully induced the cetuximab-resistant 5-8F/Erbitux hNPC cells. After treatment with cetuximab for 3 and 5 days, the RI was 1.2 and 1.1, respectively. The 5-8F/Erbitux cells showed cross-resistance to 5-FU (P<0.01) and some resistance to Taxol (P>0.05) as well as enhanced sensitivity to DDP (P>0.05). The cells had increased levels of P-gP, IGF-1R, P-IGF-1R, K-ras, H-ras, and PTEN protein expression (P<0.001), while survivin decreased (P<0.001). Through sequence alignments, gene mutations in the PTEN gene at exons 5, 7, and 8, as well as the H-ras and K-ras genes in codons 12, 13, 59, and 61, were not observed. After transfection with H-ras-shRNA plasmid, the 5-8F/Erbitux cells showed reduced levels of gene and protein expression of H-ras and elevated sensitivity to cetuximab. In conclusion, gene amplification and overexpression of H...Continue Reading
References
Sep 1, 1999·American Journal of Medical Genetics·B WeissK Shannon
Oct 8, 1999·São Paulo Medical Journal = Revista Paulista De Medicina·C M CoutinhoM A Nagai
Nov 27, 1999·Science·S Zimmermann, K Moelling
Apr 15, 2000·Gut·A I SarelaP J Guillou
Mar 10, 2001·Experimental Cell Research·L Simpson, R Parsons
May 5, 2001·The American Journal of Pathology·M MesriD C Altieri
Jun 28, 2001·Oncogene·J Mendelsohn, J Baselga
Jul 12, 2002·Nature·Gregory J Hannon
Sep 11, 2003·Head & Neck·Brigette B Y MaAnthony T C Chan
Jan 15, 2004·Cancer Science·Masashi NakamuraNaoki Watanabe
Feb 18, 2004·International Journal of Radiation Oncology, Biology, Physics·K Kian AngLuka Milas
Mar 17, 2004·Cancer Treatment Reviews·Juan Angel Fresno VaraManuel González-Barón
Apr 20, 2004·International Journal of Radiation Oncology, Biology, Physics·Daniel T T ChuaGordon K H Au
Aug 25, 2004·Cancer Cell·Yoichi NagataDihua Yu
Dec 23, 2004·Endocrine-related Cancer·H E JonesR I Nicholson
Apr 6, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Anthony T C ChanAlex Y Chang
Feb 10, 2006·The New England Journal of Medicine·James A BonnerK Kian Ang
Apr 19, 2006·Cancer Research·Alex Toker, Merav Yoeli-Lerner
Aug 4, 2006·Cancer Research·Hans-Guido WendelScott W Lowe
Aug 17, 2006·Cancer Research·Maria Y WangPaul S Mischel
Jan 27, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ingo K MellinghoffPaul S Mischel
Oct 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Chien-Hsing LuDihua Yu
Oct 16, 2007·Cancer Cell·Ben Ho Park, Nancy E Davidson
Oct 16, 2007·Cancer Cell·Katrien BernsRené Bernards
Mar 14, 2008·The New England Journal of Medicine·Fortunato Ciardiello, Giampaolo Tortora
May 28, 2008·Pharmacotherapy·Gary W Jean, Sachin R Shah
Sep 12, 2008·The New England Journal of Medicine·Jan B VermorkenRicardo Hitt
Oct 24, 2008·The New England Journal of Medicine·Christos S KarapetisJohn R Zalcberg
Nov 18, 2008·Medical Oncology·Chu-Chung ChouChin-Yuan Tzen
Feb 13, 2009·Oncology Reports·Sanae BoualiJean-Louis Merlin
Apr 16, 2009·BMC Cancer·Jean-Luc RaoulPhilippe Rougier
Jul 10, 2009·Annals of Oncology : Official Journal of the European Society for Medical Oncology·E Van CutsemUNKNOWN ESMO Guidelines Working Group
Jul 29, 2009·Nature Reviews. Clinical Oncology·Nicola NormannoFortunato Ciardiello
Jul 29, 2009·Journal of Oncology·Ann Marie Egloff, Jennifer Rubin Grandis
Aug 12, 2009·Current Drug Targets·F MeriggiA Zaniboni
Citations
Jul 4, 2013·The Oncologist·Carolien BoeckxFilip Lardon
Jan 28, 2015·Molecular Medicine Reports·Xin LiXiujuan Qu
May 24, 2011·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Qiang ZuoWangjun Liao
Dec 23, 2011·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Qiang ZuoWangjun Liao
Aug 2, 2018·Cancer Biology & Therapy·Kun WangBin Yi
Feb 27, 2019·Targeted Oncology·Pei San YeeSok Ching Cheong
Aug 23, 2019·Scientific Reports·Katsuhiro UzawaHideki Tanzawa
Jun 1, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Shilpa BhatiaSana D Karam
Mar 16, 2021·Frontiers in Oncology·Sandra Ortiz-CuaranPierre Saintigny