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

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 24h 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, these results suggest targeting IGF-1R by PPP may represent a new strategy for treatment of NPCs with positive IGF-1R expression.

• Authors: Shu-Cheng Yin, Wei Guo, Ze-Zhang Tao
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 439 Issue 1 Pg. 1-5 (Sep 13 2013) ISSN: 1090-2104 [Electronic] United States
• PMID: 23973483 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Somatomedins
• picropodophyllin
• Receptor, IGF Type 1
• Proto-Oncogene Proteins c-akt
• Podophyllotoxin

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Carcinoma
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Humans
• Inhibitory Concentration 50
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms (drug therapy)
• Neoplasm Metastasis
• Phosphorylation
• Podophyllotoxin (analogs & derivatives, pharmacology)
• Proto-Oncogene Proteins c-akt (metabolism)
• Receptor, IGF Type 1 (antagonists & inhibitors, metabolism)
• Somatomedins (metabolism)
• Xenograft Model Antitumor Assays