Adenovirus-mediated eukaryotic initiation factor 4E binding protein-1 in combination with rapamycin inhibits tumor growth of pancreatic ductal adenocarcinoma in vivo

Mishra, Roshan; Miyamoto, Masaki; Yoshioka, Tatsuya; Ishikawa, Keidai; Matsumura, Yoshiyuki; Shoji, Yasuhito; Ichinokawa, Kazuomi; Itoh, Tommo; Shichinohe, Toshiaki; Hirano, Satoshi; Kondo, Satoshi

Adenovirus-mediated eukaryotic initiation factor 4E binding protein-1 in combination with rapamycin inhibits tumor growth of pancreatic ductal adenocarcinoma in vivo

Mishra, Roshan; Miyamoto, Masaki; Yoshioka, Tatsuya et al.

International Journal of Oncology, 2009, 34(5), 1231-1240

Permalink : https://hdl.handle.net/2115/43022

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アクセス権	open access
URI	https://hdl.handle.net/2115/43022
タイトル	Adenovirus-mediated eukaryotic initiation factor 4E binding protein-1 in combination with rapamycin inhibits tumor growth of pancreatic ductal adenocarcinoma in vivo
著者	Mishra, Roshan ; Miyamoto, Masaki ; Yoshioka, Tatsuya ; Ishikawa, Keidai ; Matsumura, Yoshiyuki ; Shoji, Yasuhito ; Ichinokawa, Kazuomi ; Itoh, Tommo ; Shichinohe, Toshiaki ; Hirano, Satoshi ; Kondo, Satoshi
著者名 Mishra, Roshan
e-Rad_Researcher 40333611 著者名 Miyamoto, Masaki
著者名 Yoshioka, Tatsuya
著者名 Ishikawa, Keidai
著者名 Matsumura, Yoshiyuki
著者名 Shoji, Yasuhito
著者名 Ichinokawa, Kazuomi
著者名 Itoh, Tommo
e-Rad_Researcher 70374353 著者名 Shichinohe, Toshiaki
e-Rad_Researcher 50322813 著者名 Hirano, Satoshi
e-Rad_Researcher 30215454 著者名 Kondo, Satoshi
言語	英語
キーワード	eIF4E
	translation repressor protein 4E-BP1
	translation initiation factor
	pancreatic ductal adenocarcinoma
	rapamycin
発行日	2009-05
出版者	Spandidos Publications
収録物名	International Journal of Oncology
巻(号)	34(5)
ページ	1231-1240
抄録	Over-expression of eIF4E indicates a poor prognosis in different tumors. In the present study, we investigated the frequency of eIF4E, 4E-BP1 and phosphorylated 4E-BP1 expression in PDAC cell lines, gastric carcinoma (GC) cell lines and human embryonic pancreatic cells, as well as gene therapy using translation repressor gene 4E-BP1 in combination with the mTOR inhibitor rapamycin. We also assessed the significance of eIF4E expression in 80 PDAC cases. Combination therapy of adenovirus vector-delivered 4E-BP1 gene and rapamycin was administered to determine their growth inhibition effect in vitro and in vivo in mice. Our study revealed that all PDAC cell lines, GC cell lines and human embryonic pancreas-derived cells expressed the 25-kDa eIF4E protein (MIAPaca-2 cells also expressed the 13-kDa protein 4E-BP1). The 80 PDAC specimens showed a heterogeneous pattern of eIF4E staining. No significant correlation between eIF4E expression and TNM classification was found. Adenovirus vectors Ad-4E-BP1 and Ad-GFP efficiently showed transgenic expression with hyperphosphorylation of 4E-BP1; however, insignificant growth inhibition of the PDAC and GC cell lines was observed. Combination therapy with rapamycin significantly inhibited proliferation and tumor growth in vitro as well as in vivo. Therefore, combination of Ad 4E-BP1 and rapamycin may be a more effective adjuvant therapy
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
PISSN	1019-6439
EISSN	1791-2423
関連情報	PMID 19360336
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.3892/ijo_00000251