γ-H2AX as a DNA damage marker to evaluate Suramin sensitization effect on Cisplatin in pancreatic cancer xenograft
Advisor:Au, Jessie Lai-Sim
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Publisher:The Ohio State University
Series/Report no.:The Ohio State University. Department of Pharmaceutical Sciences Honors Theses; 2008
Purpose: γ-H2AX, a DNA double strand break marker, was used to evaluate suramin sensitization effect in cisplatin-treated Capan-1-bearing mice xenografts. Methods: Mice bearing pancreatic cancer Capan-1 subcutaneous xenografts were treated with control vehicle, cisplatin (7.5mg/kg), suramin (10mg/kg) combined with cisplatin, or suramin (100mg/kg) combined with cisplatin. Tumor samples were taken on 45th day after initiation of treatment. DNA damage after drug treatment was evaluated using immunohistochemical staining with γ -H2AX antibody. Results: In terms of tumor growth, suramin at low dose enhanced tumor size shrinkage and delayed tumor regrowth compared to cisplatin alone, while high dose suramin antagonized cisplatin effect. Low dose suramin induced more DNA damage indicated by γ-H2AX positive staining; it is not significantly different from the cisplatin group though. Conclusions: Present study identified the sensitization effect of low dose suramin on cisplatin-treated pancreatic cancer Capan-1 xenografts by inducing more tumor shrinkage and prolonged tumor regrowth delay. In addition, low dose suramin caused more DNA damage retaining indicated by higher level of γ-H2AX positive cells. This result serves as a preliminary study to use γ-H2AX as a DNA damage repair marker to evaluate suramin sensitization effect in DNA damaging agents.
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