Tumor Growth Suppression and Enhanced Radioresponse by an Exogenous Epidermal Growth Factor in Mouse Xenograft Models with A431 Cells

Cancer Res Treat. 2015 Oct;47(4):921-30. doi: 10.4143/crt.2014.153. Epub 2015 Jan 7.

Abstract

Purpose: The purpose of this study was to evaluate whether an exogenous epidermal growth factor (EGF) could induce anti-tumor and radiosensitizing effects in vivo.

Materials and methods: BALB/c-nu mice that were inoculated with A431 (human squamous cell carcinoma) cells in the right hind legs were divided into five groups: I (no treatment), II (EGF for 6 days), III (EGF for 20 days), IV (radiotherapy [RT]), and V (RT plus concomitant EGF). EGF was administered intraperitoneally (5 mg/kg) once a day and the RT dose was 30 Gy in six fractions. Hematoxylin and eosin (H&E) stained sections of tumor, liver, lung, and kidney tissues were investigated. Additionally, tumors were subjected to immunohistochemistry staining with caspase-3.

Results: EGF for 6 days decreased tumor volume, but it approached the level of the control group at the end of follow-up (p=0.550). The duration of tumor shrinkage was prolonged in group V while the slope of tumor re-growth phase was steeper in group IV (p=0.034). EGF for 20 days decreased tumor volume until the end of the observation period (p < 0.001). Immunohistochemistry revealed that mice in group V showed stronger intensity than those in group IV. There were no abnormal histological findings upon H&E staining of the normal organs.

Conclusion: EGF-induced anti-tumor effect was ascertained in the xenograft mouse models with A431 cells. Concomitant use of EGF has the potential role as a radiosensitizer in the design of fractionated irradiation.

Keywords: Antineoplastic agents; Apoptosis; Epidermal growth factor; Radiation-sensitizing agents; Xenograft model antitumor assays.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / radiotherapy*
  • Cell Line, Tumor
  • Epidermal Growth Factor / administration & dosage
  • Epidermal Growth Factor / therapeutic use*
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / radiotherapy*
  • Radiotherapy*

Substances

  • Epidermal Growth Factor