Abstract
Sorafenib is the first FDA-approved therapeutic drug for molecular target medication on advanced-stage hepatocellular carcinoma. It is reported that sorafenib could improve the survival of progression-free patients for 4 to 6 months; however, most of the patients developed drug resistance. Thus, it is critical to reveal the biological mechanisms behind sorafenib resistance. In this study, a sorafenib-resistant model was developed by exposing HepG2 cells to sorafenib with gradient increasing concentration, and the resistance-related genes were screened by microarray. Real-time qPCR was used to validate selected gene expression of the resistance model, and lentivirus vector-mediated RNA interference was applied for specific gene knockdown. In addition, high-throughput High Celigo Select (HCS) and flow cytometry were used to measure the effect on cellular proliferation and apoptosis. As a result, our study established a sorafenib-resistant model with IC50 of 9.988 μM. The Affymetrix expression profile of the sorafenib-resistant model showed 35 resistant-related genes, and 91.4% of the resistant genes showed upregulation in HepG2 resistance cells. In addition, 20 genes were knocked down to measure cell proliferation, and MAP4K3 wit...Continue Reading
References
May 18, 2001·British Journal of Cancer·Y ItoN Matsuura
Jul 10, 2009·The Lancet Oncology·Sandrine FaivreAnn Lii Cheng
Feb 5, 2010·Anti-cancer Drugs·Alfredo Carrato MenaCarmen Guillén-Ponce
Jun 25, 2010·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·Silvia TremosiniJordi Bruix
May 27, 2011·Cancer Research·Christine M LovlyWilliam Pao
Jul 28, 2011·Cancer Research·Takaaki SasakiPasi A Jänne
Feb 22, 2012·Cancer Science·Daiki MikiKazuaki Chayama
May 19, 2012·British Journal of Cancer·S HagiwaraT Sakurai
Jun 26, 2012·Journal of Hepatology·Jordi BruixJosep M Llovet
Feb 1, 2013·Journal of Virology·Seungtaek KimStanley M Lemon
Aug 27, 2013·Lancet·Rafael RosellNiki Karachaliou
Apr 8, 2014·Molecular Cancer Therapeutics·Bo ZhaiXueying Sun
Jun 7, 2014·PloS One·Xiao-Dong LiangSheng-Lin Ma
Aug 30, 2014·Cancer Biomarkers : Section a of Disease Markers·Hui TangKangling Zhang
Feb 26, 2016·World Journal of Gastrointestinal Oncology·Kiruthikah ThillaiDebashis Sarker
Dec 26, 2016·Biochemical Pharmacology·Wei-Jian SunZhi-Qiang Zheng
Mar 28, 2017·Acta Pharmacologica Sinica·Yan-Jing ZhuLei Chen
Nov 16, 2017·Oncotarget·Raymond Kwok Kei ChowXin-Yuan Guan
Sep 1, 2018·Oncogene·Jing SunWenge Zhu
Apr 30, 2019·Cancer Communications·Rui-Mei FengRui-Hua Xu
Aug 23, 2019·Cancer Research·Yi ZhangWenge Zhu