PMID- 28476786 OWN - NLM STAT- MEDLINE DCOM- 20170810 LR - 20170810 IS - 1791-7530 (Electronic) IS - 0250-7005 (Linking) VI - 37 IP - 5 DP - 2017 May TI - Amphiregulin as a Novel Resistance Factor for Amrubicin in Lung Cancer Cells. PG - 2225-2231 AB - BACKGROUND/AIM: Amrubicin (AMR) has shown promising activity for lung cancer. However, little is known about the mechanism underlying resistance to this agent. The aim of this study was to elucidate the mechanism underlying resistance to AMR. MATERIALS AND METHODS: We first developed amrubicinol (AMR-OH)-resistant cell lines (H520/R and DMS53/R) by exposing lung cancer cell lines (H520 and DMS53) to increasing concentrations of AMR-OH and performed functional analysis by using these cell lines. RESULTS: Transcriptome analyses showed that amphiregulin (AREG) was the most highly up-regulated gene in both AMR-OH-resistant cell lines compared to parent cells. Conditioned medium from DMS53/R cells reduced the sensitivity to AMR-OH in DMS53 cells. In contrast, DMS53/R cells transfected with siRNA directed against AREG recovered their sensitivity to AMR-OH. An additional administration of cetuximab with amrubicinol also restored the sensitivity to AMR-OH. CONCLUSION: Amphiregulin plays an important role in resistance to AMR-OH. CI - Copyright(c) 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved. FAU - Tokunaga, Shuntaro AU - Tokunaga S AD - Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. FAU - Nagano, Tatsuya AU - Nagano T AD - Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan tnagano@med.kobe-u.ac.jp. FAU - Kobayashi, Kazuyuki AU - Kobayashi K AD - Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. FAU - Katsurada, Masahiro AU - Katsurada M AD - Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. FAU - Nakata, Kyosuke AU - Nakata K AD - Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. FAU - Yamamoto, Masatsugu AU - Yamamoto M AD - Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. FAU - Tachihara, Motoko AU - Tachihara M AD - Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. FAU - Kamiryo, Hiroshi AU - Kamiryo H AD - Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. FAU - Yokozaki, Hiroshi AU - Yokozaki H AD - Division of Pathology, Department of Pathology, Kobe University Graduate School of Medicine, Kobe, Japan. FAU - Nishimura, Yoshihiro AU - Nishimura Y AD - Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. LA - eng PT - Journal Article PL - Greece TA - Anticancer Res JT - Anticancer research JID - 8102988 RN - 0 (Amphiregulin) RN - 0 (Anthracyclines) RN - 0 (Antineoplastic Agents) RN - 0 (RNA, Small Interfering) RN - 0 (amrubicinol) RN - 93N13LB4Z2 (amrubicin) SB - IM MH - Amphiregulin/*genetics MH - Animals MH - Anthracyclines/*pharmacology/therapeutic use MH - Antineoplastic Agents/*pharmacology/therapeutic use MH - Cell Line, Tumor MH - Drug Resistance, Neoplasm/*genetics MH - Female MH - Humans MH - Lung Neoplasms/drug therapy/*genetics/pathology MH - Mice, Inbred BALB C MH - Mice, Nude MH - RNA, Small Interfering MH - Tumor Burden/drug effects OTO - NOTNLM OT - Amrubicin OT - amphiregulin OT - cetuximab OT - lung cancer EDAT- 2017/05/10 06:00 MHDA- 2017/08/11 06:00 CRDT- 2017/05/07 06:00 PHST- 2017/03/22 00:00 [received] PHST- 2017/04/01 00:00 [revised] PHST- 2017/04/03 00:00 [accepted] PHST- 2017/05/07 06:00 [entrez] PHST- 2017/05/10 06:00 [pubmed] PHST- 2017/08/11 06:00 [medline] AID - 37/5/2225 [pii] AID - 10.21873/anticanres.11558 [doi] PST - ppublish SO - Anticancer Res. 2017 May;37(5):2225-2231. doi: 10.21873/anticanres.11558.