Tumor Growth Suppression and Enhanced Radioresponse by an Exogenous Epidermal Growth Factor in Mouse Xenograft Models with A431 Cells
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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 MethodsBALB/c-nu mice that were inoculated with A431 (human squamous cell carcinoma) cellsin 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 administeredintraperitoneally (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 wereinvestigated. Additionally, tumors were subjected to immunohistochemistry staining withcaspase-3. ResultsEGF for 6 days decreased tumor volume, but it approached the level of the control group atthe end of follow-up (p=0.550). The duration of tumor shrinkage was prolonged in group Vwhile the slope of tumor re-growth phase was steeper in group IV (p=0.034). EGF for 20days decreased tumor volume until the end of the observation period (p < 0.001). Immunohistochemistryrevealed that mice in group V showed stronger intensity than those in groupIV. There were no abnormal histological findings upon H&E staining of the normal organs. ConclusionEGF-induced anti-tumor effect was ascertained in the xenograft mouse models with A431cells. Concomitant use of EGF has the potential role as a radiosensitizer in the design offractionated irradiation.
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 MethodsBALB/c-nu mice that were inoculated with A431 (human squamous cell carcinoma) cellsin 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 administeredintraperitoneally (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 wereinvestigated. Additionally, tumors were subjected to immunohistochemistry staining withcaspase-3. ResultsEGF for 6 days decreased tumor volume, but it approached the level of the control group atthe end of follow-up (p=0.550). The duration of tumor shrinkage was prolonged in group Vwhile the slope of tumor re-growth phase was steeper in group IV (p=0.034). EGF for 20days decreased tumor volume until the end of the observation period (p < 0.001). Immunohistochemistryrevealed that mice in group V showed stronger intensity than those in groupIV. There were no abnormal histological findings upon H&E staining of the normal organs. ConclusionEGF-induced anti-tumor effect was ascertained in the xenograft mouse models with A431cells. Concomitant use of EGF has the potential role as a radiosensitizer in the design offractionated irradiation.
참고문헌 (23)
- Boonstra J, "The epidermal growth factor", Cell Biol Int, 19, pp.413~430 (1995)
- Henson ES, "Surviving cell death through epidermal growth factor(EGF)signal transduction pathways : implications for cancer therapy", Cell Signal, 18, pp.2089~2097 (2006)
- Cao L, "Epidermal growth factor induces cell cycle arrest and apoptosis of squamous carcinoma cells through reduction of cell adhesion", J Cell Biochem, 77, pp.569~583 (2000)
- Song JY, "Epidermal growth factor competes with EGF receptor inhibitors to induce cell death in EGFR-overexpressing tumor cells", Cancer Lett, 283, pp.135~142 (2009)
- Worthylake R, "Structural aspects of the epidermal growth factor receptor required for transmodulation of erbB-2", neu, 1997, pp.272, 8594~8601
- Rush JS, "Endosomal accumulation of the activated epidermal growth factor receptor(EGFR)induces apoptosis", J Biol Chem, 287, pp.712~722 (2012)
- Kozyulina PY, "p38 MAP kinase enhances EGF-induced apoptosis in A431carcinoma cells by promoting tyrosine phosphorylation of STAT1", Biochem Biophys Res Commun, 430, pp.331~335 (2013)
- Grudinkin PS, "EGF-induced apoptosis in A431 cells is dependent on STAT1, but not on STAT3", Eur J Cell Biol, 86, pp.591~603 (2007)
- Ciardiello F, "EGFR antagonists in cancer treatment", N Engl J Med, 358, pp.1160~1174 (2008)
- Nyati MK, "Integration of EGFR inhibitors with radiochemotherapy", Nat Rev Cancer, 6, pp.876~885 (2006)
- Huang SM, "Modulation of radiation response after epidermal growth factor receptor blockade in squamous cell carcinomas : inhibition of damage repair, cell cycle kinetics, and tumor angiogenesis", Clin Cancer Res, 6, pp.2166~2174 (2000)
- Bonner JA, "Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer : 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival", Lancet Oncol, 11, pp.21~28 (2010)
- Kwok TT, "Enhancement of sensitivity of human squamous carcinoma cells to radiation by epidermal growth factor", J Natl Cancer Inst, 81, pp.1020~1024 (1989)
- Kwok TT, "Differences in EGF related radiosensitisation of human squamous carcinoma cells with high and low numbers of EGF receptors", Br J Cancer, 64, pp.251~254 (1991)
- Bonner JA, "The interaction of epidermal growth factor and radiation in human head and neck squamous cell carcinoma cell lines with vastly different radiosensitivities", Int J Radiat Oncol Biol Phys, 29, pp.243~247 (1994)
- Licitra L, "Role of EGFR family receptors in proliferation of squamous carcinoma cells induced by wound healing fluids of head and neck cancer patients", Ann Oncol, 22, pp.1886~1893 (2011)
- Choi J, "Epidermal growth factor induces cell death in the absence of overexpressed epidermal growth factor receptor and ErbB2 in various human cancer cell lines", Cancer Invest, 28, pp.505~514 (2010)
- Kwok TT, "Cell cycle dependence of epidermal growth factor induced radiosensitization", Int J Radiat Oncol Biol Phys, 22, pp.525~527 (1992)
- Kwon EK, "Differential effects of recombinant human EGF on proliferation and radiation survival of normal fibroblast and cancer cell lines", Open Transl Med J, 1, pp.9~15 (2009)
- Chiu B, "Novel action of epidermal growth factor on caspase 3 and its potential as a chemotherapeutic adjunct for neuroblastoma", J Pediatr Surg, 42, pp.1389~1395 (2007)
- Fan Z, "Prolonged induction of p21Cip1", WAF1, PCNA complex by epidermal growth factor receptor activation mediates ligand-induced A431 cell growth inhibition, pp.J Cell Biol, 1995[DOI]
- Jakus J, "Growth inhibitory concentrations of EGF induce p21(WAF1", Cip1)and alter cell cycle control in squamous carcinoma cells, 1996, pp.12, 2369~2376
- Bromberg JF, "Epidermal growth factor-induced growth inhibition requires Stat1 activation", Cell Growth Differ, 9, pp.505~512 (1998)
