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Title: Picropodophyllin inhibits tumor growth of human nasopharyngeal carcinoma in a mouse model

Highlights: •We identified that PPP inhibits IGF-1R/Akt pathway in NPC cells. •PPP dose-dependently inhibits NPC cell proliferation in vitro. •PPP suppresses tumor growth of NPC in nude mice. •PPP have little effect on microtubule assembly. -- Abstract: Insulin-like growth factor-1 receptor (IGF-1R) is a cell membrane receptor with tyrosine kinase activity and plays important roles in cell transformation, tumor growth, tumor invasion, and metastasis. Picropodophyllin (PPP) is a selective IGF-1R inhibitor and shows promising antitumor effects for several human cancers. However, its antitumor effects in nasopharyngeal carcinoma (NPC) remain unclear. The purpose of this study is to investigate the antitumor activity of PPP in NPC using in vitro cell culture and in vivo animal model. We found that PPP dose-dependently decreased the IGF-induced phosphorylation and activity of IGF-1R and consequently reduced the phosphorylation of Akt, one downstream target of IGF-1R. In addition, PPP inhibited NPC cell proliferation in vitro. The half maximal inhibitory concentration (IC50) of PPP for NPC cell line CNE-2 was ⩽1 μM at 24 h after treatment and ⩽0.5 μM at 48 h after treatment, respectively. Moreover, administration of PPP by intraperitoneal injection significantly suppressed the tumor growth of xenografted NPC in nude mice. Taken together, thesemore » results suggest targeting IGF-1R by PPP may represent a new strategy for treatment of NPCs with positive IGF-1R expression.« less
Authors:
 [1] ;  [2] ;  [3] ;  [1]
  1. Department of Otolaryngology – Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan 430060 (China)
  2. (China)
  3. Department of Otolaryngology – Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China)
Publication Date:
OSTI Identifier:
22242088
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 439; Journal Issue: 1; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CARCINOMAS; CELL CULTURES; CELL MEMBRANES; CELL PROLIFERATION; CELL TRANSFORMATIONS; CONCENTRATION RATIO; GROWTH FACTORS; IN VITRO; INSULIN; INTRAPERITONEAL INJECTION; MICE; MICROTUBULES; PHOSPHORYLATION; RECEPTORS; TYROSINE