Analysis of resistance mechanism to amrubicin

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461158
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Kobe University
• Principal Investigator: Tachihara Motoko 神戸大学, 医学(系)研究科(研究院), 助教 (40448626)
• Co-Investigator(Kenkyū-buntansha): NISHIMURA YOSHIHIRO 神戸大学, 医学部附属病院, 教授 (20291453) ; KOBAYASHI KAZUYUKI 神戸大学, 大学院医学研究科, 講師 (50403275) ; TAMURA DAISUKE 神戸大学, 医学部附属病院, 特定助教 (80646597) ; NAGANO TATSUYA 神戸大学, 大学院医学研究科, 特命助教 (80624684)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: アムルビシン / 薬剤耐性 / アンフィレグリン

Outline of Final Research Achievements

Amrubicin (AMR) has shown promising activity for lung cancer. However, little is known about the mechanism of resistance for this agent.
Transcriptome analysis of amrubicinol (AMR-OH)-resistant lung cancer cell lines (H520/R, and DMS53/R) showed that amphiregulin (AREG) was most highly up-regulated gene in both of the AMR-OH-resistant cells compared to H520 and DMS53. AREG concentration in cultured medium of DMS53/R was higher compared to DMS53 after 72h culture with AMR-OH. A conditioned medium from DMS53/R decreased sensitivity to AMR-OH in DMS53. On the other hand, DMS53/R transfected with siRNA directed against AREG recovered sensitivity to AMR-OH. Additional administration of cetuximab (CET) on AMR-OH also recovered sensitivity to AMR-OH in DMS53/R. AMR/CET treatment showed higher antitumor activity in DMS53/R-bearing mice than AMR treatment.

Free Research Field

呼吸器内科