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

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Title: Adenovirus-mediated eukaryotic initiation factor 4E binding protein-1 in combination with rapamycin inhibits tumor growth of pancreatic ductal adenocarcinoma in vivo
Authors: Mishra, Roshan Browse this author
Miyamoto, Masaki Browse this author →KAKEN DB
Yoshioka, Tatsuya Browse this author
Ishikawa, Keidai Browse this author
Matsumura, Yoshiyuki Browse this author
Shoji, Yasuhito Browse this author
Ichinokawa, Kazuomi Browse this author
Itoh, Tommo Browse this author
Shichinohe, Toshiaki Browse this author →KAKEN DB
Hirano, Satoshi Browse this author →KAKEN DB
Kondo, Satoshi Browse this author →KAKEN DB
Keywords: eIF4E
translation repressor protein 4E-BP1
translation initiation factor
pancreatic ductal adenocarcinoma
rapamycin
Issue Date: May-2009
Publisher: Spandidos Publications
Journal Title: International Journal of Oncology
Volume: 34
Issue: 5
Start Page: 1231
End Page: 1240
Publisher DOI: 10.3892/ijo_00000251
PMID: 19360336
Abstract: 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
Type: article
URI: http://hdl.handle.net/2115/43022
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: Roshan Mishra

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