Paula B Caffrey1, Gerald D Frenkel2, Kathryn L McAndrew3, Kenneth Marks4. 1. Department of Biological and Environmental Sciences, California University of PA, California, PA, U.S.A. caffrey@calu.edu. 2. Department of Biological Sciences, Rutgers University, Newark, NJ, U.S.A. 3. Department of Biological and Environmental Sciences, California University of PA, California, PA, U.S.A. 4. Magee Women's Research Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, U.S.A.
Abstract
BACKGROUND/AIM: To study the prevention of chemotherapy resistance, we have previously designed models of drug-resistant ovarian cancer. We here report an in vivo model of cisplatin-resistant small cell lung cancer (SCLC). MATERIALS AND METHODS: Mice bearing H526 SCLC xenografts received intraperitoneal pretreatment with a sub-effective cisplatin dose (0.75-1.5 mg/kg) or no pretreatment (controls). Seven days later, all mice received a higher cisplatin dose (3.0 mg/kg), and tumor response was recorded. Cell cultures initiated from pretreated and control xenografts were tested for cisplatin resistance and for glutathione-S-transferase (GST) activity. RESULTS: Pretreatment with 1.5 mg/kg cisplatin induced resistance to 3.0 mg/kg cisplatin. Cells from a pretreated tumor were cisplatin resistant and had nearly twice the GST activity as cells from a control tumor. CONCLUSION: Such cells may prove useful for identifying other resistance mechanisms and thus guide the selection of potential preventative agents to be tested in the in vivo model.
BACKGROUND/AIM: To study the prevention of chemotherapy resistance, we have previously designed models of drug-resistant ovarian cancer. We here report an in vivo model of cisplatin-resistant small cell lung cancer (SCLC). MATERIALS AND METHODS:Mice bearing H526 SCLC xenografts received intraperitoneal pretreatment with a sub-effective cisplatin dose (0.75-1.5 mg/kg) or no pretreatment (controls). Seven days later, all mice received a higher cisplatin dose (3.0 mg/kg), and tumor response was recorded. Cell cultures initiated from pretreated and control xenografts were tested for cisplatin resistance and for glutathione-S-transferase (GST) activity. RESULTS: Pretreatment with 1.5 mg/kg cisplatin induced resistance to 3.0 mg/kg cisplatin. Cells from a pretreated tumor were cisplatin resistant and had nearly twice the GST activity as cells from a control tumor. CONCLUSION: Such cells may prove useful for identifying other resistance mechanisms and thus guide the selection of potential preventative agents to be tested in the in vivo model.