論文 - 詳細
| RRC ID | 71807 |
|---|---|
| 著者 | Omori M, Noro R, Seike M, Matsuda K, Hirao M, Fukuizumi A, Takano N, Miyanaga A, Gemma A. |
| タイトル | Inhibitors of ABCB1 and ABCG2 overcame resistance to topoisomerase inhibitors in small cell lung cancer. |
| ジャーナル | Thorac Cancer |
| Abstract |
BACKGROUND:Small cell lung cancer (SCLC) is a highly aggressive disease with a poor prognosis. Although most patients initially respond to topoisomerase inhibitors, resistance rapidly emerges. The aim, therefore, is to overcome resistance to topoisomerase I (irinotecan) or II (etoposide) inhibitors in SCLCs. METHODS:To identify key factors in the chemoresistance of SCLCs, we established four cell lines resistant to etoposide or an active metabolite of irinotecan, SN-38, from SCLC cell lines and evaluated RNA profiles using parental and newly established cell lines. RESULTS:We found that the drug efflux protein, ATP-binding cassette sub-family B member 1 (ABCB1), was associated with resistance to etoposide, and ATP-binding cassette sub-family G member 2 (ABCG2) was associated with resistance to SN-38 by RNA sequencing. The inhibition of ABCB1 or ABCG2 in each resistant cell line induced synergistic apoptotic activity and promoted drug sensitivity in resistant SCLC cells. The ABC transporter inhibitors, elacridar and tariquidar, restored sensitivity to etoposide or SN-38 in in vitro and in vivo studies, and promoted apoptotic activity and G2-M arrest in resistant SCLC cells. CONCLUSIONS:ABC transporter inhibitors may be a promising therapeutic strategy for the purpose of overcoming resistance to topoisomerase inhibitors in patients with SCLC. |
| 巻・号 | 13(15) |
| ページ | 2142-2151 |
| 公開日 | 2022-8-1 |
| DOI | 10.1111/1759-7714.14527 |
| PMID | 35719112 |
| PMC | PMC9346178 |
| MeSH | ATP Binding Cassette Transporter, Subfamily B / antagonists & inhibitors ATP Binding Cassette Transporter, Subfamily B / genetics ATP Binding Cassette Transporter, Subfamily G, Member 2 / antagonists & inhibitors ATP Binding Cassette Transporter, Subfamily G, Member 2 / genetics Antineoplastic Agents* / pharmacology Apoptosis Cell Line, Tumor Drug Resistance, Neoplasm Etoposide / pharmacology G2 Phase Cell Cycle Checkpoints Humans Irinotecan / pharmacology Lung Neoplasms* / drug therapy Lung Neoplasms* / genetics Neoplasm Proteins / genetics Neoplasm Proteins / metabolism Small Cell Lung Carcinoma* / drug therapy Small Cell Lung Carcinoma* / genetics Topoisomerase Inhibitors / pharmacology |
| IF | 2.524 |
| リソース情報 | |
| ヒト・動物細胞 | MS-1(RCB0725) Lu-139(RCB0469) |