Adenovirus-E1A gene therapy enhances the in vivo sensitivity of Ewing's sarcoma to VP-16.

Abstract

This study determined the effect of Ad-E1A gene therapy in vivo. TC71 cells (2 x 10(6)) injected subcutaneously into nude mice resulted in tumor development (1-3 mm) 6 days later. Animals were then treated with Ad-E1A or Ad-beta-gal (5 x 10(9) plaque-forming units) by intratumoral injection twice weekly for 2 weeks. Animals received 8 mg/kg VP-16 given by intraperitoneal injection daily for 5 days following the first week of treatment with Ad-E1A or Ad-beta-gal. Control animals received no therapy or VP-16 only after tumor cells were injected. When tumors exceeded 2 x 2 cm, the mice were sacrificed and the tumors underwent histologic and immunohistochemical analysis. Tumors from mice treated with Ad-E1A plus VP-16 were 9.6-fold smaller than those treated with VP-16 alone and 6.3-fold smaller than those treated with Ad-E1A alone. HER2/neu p185 protein expression decreased in all tumors that received Ad-E1A therapy. TUNEL fluorescence staining revealed more apoptosis in the tumors from animals treated with Ad-E1A plus VP-16 than in those from animals treated with Ad-E1A alone, Ad-beta-gal plus VP-16, or VP-16 alone. These data demonstrated that Ad-E1A gene therapy down-regulated HER2/neu expression, increased tumor cell apoptosis induced by VP-16, and enhanced tumor cell sensitivity to VP-16. Ad-E1A may have potential in the treatment of relapsed drug-resistant Ewing's sarcoma.

• Authors: Rong-Rong Zhou, Shu-Fang Jia, Zhichao Zhou, Yunfang Wang, Corazon D Bucana, Eugenie S Kleinerman
• Journal: Cancer gene therapy (Cancer Gene Ther) Vol. 9 Issue 5 Pg. 407-13 (May 2002) ISSN: 0929-1903 [Print] England
• PMID: 11961663 (Publication Type: Journal Article)

Chemical References

• Adenovirus E1A Proteins
• Antineoplastic Agents, Phytogenic
• Etoposide
• Receptor, ErbB-2

Topics

• Adenoviridae (genetics)
• Adenovirus E1A Proteins (genetics)
• Animals
• Antineoplastic Agents, Phytogenic (therapeutic use)
• Apoptosis
• Down-Regulation
• Etoposide (metabolism, therapeutic use)
• Genetic Therapy (methods)
• Humans
• Immunohistochemistry
• In Situ Nick-End Labeling
• Mice
• Mice, Nude
• Microscopy, Fluorescence
• Models, Genetic
• Receptor, ErbB-2 (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Sarcoma, Ewing (therapy)
• Time Factors
• Tumor Cells, Cultured