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ID 49562
フルテキストURL
著者
Rai, Kammei Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
Takigawa, Nagio Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
Ito, Sachio Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Mol Genet Kaken ID publons researchmap
Kashihara, Hiromi Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
Ichihara, Eiki Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med Kaken ID publons
Yasuda, Tatsuji Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Cell Chem
Shimizu, Kenji Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Mol Genet
Tanimoto, Mitsune Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med Kaken ID publons researchmap
Kiura, Katsuyuki Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med ORCID Kaken ID publons researchmap
抄録
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) have been strikingly effective in lung cancers harboring activating EGFR mutations. Unfortunately, the cancer cells eventually acquire resistance to EGFR-TKI. Approximately 50% of the acquired resistance involves a secondary T790M mutation. To overcome the resistance, we focused on EGFR suppression using microRNA-7 (miR-7), targeting multiple sites in the 30-untranslated region of EGFR mRNA. Two EGFR-TKI-sensitive cell lines (PC-9 and H3255) and two EGFR-TKI-resistant cell lines harboring T790M (RPC-9 and H1975) were used. We constructed miR-7-2 containing miR-7-expressing plasmid. After transfection of the miR-7-expressing plasmid, using cationic liposomes, a quantitative PCR and dual luciferase assay were conducted to examine the efficacy. The antiproliferative effect was evaluated using a cell count assay and xenograft model. Protein expression was examined by Western blotting. The miR-7 expression level of the transfectants was approximately 30-fold higher, and the luciferase activity was ablated by 92%. miR-7 significantly inhibited cell growth not only in PC-9 and H3255 but also in RPC-9 and H1975. Expression of insulin receptor substrate-1 (IRS-1), RAF-1, and EGFR was suppressed in the four cell lines. Injection of the miR-7-expressing plasmid revealed marked tumor regression in a mouse xenograft model using RPC-9 and H1975. EGFR, RAF-1, and IRS-1 were suppressed in the residual tumors. These findings indicate promising therapeutic applications of miR-7-expressing plasmids against EGFR oncogene-addicted lung cancers including T790M resistance by liposomal delivery. Mol Cancer Ther; 10(9); 1720-7.
発行日
2011-09
出版物タイトル
Molecular Cancer Therapeutics
10巻
9号
開始ページ
1720
終了ページ
1727
ISSN
1535-7163
資料タイプ
学術雑誌論文
オフィシャル URL
http://dx.doi.org/10.1158/1535-7163.MCT-11-0220
言語
English
著作権者
(C)2011 AACR.
論文のバージョン
author
査読
有り
DOI
Web of Science KeyUT