A Model of the Development of Cisplatin Resistance in Human Small Cell Lung Cancer Xenografts.
OBJECTIVE
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).


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.


CONCLUSIONS
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.
Department of Biological and Environmental Sciences, California University of PA, California, PA, U.S.A. caffrey@calu.edu.
Paula B
PB
Caffrey
Department of Biological Sciences, Rutgers University, Newark, NJ, U.S.A.
Gerald D
GD
Frenkel
Department of Biological and Environmental Sciences, California University of PA, California, PA, U.S.A.
Kathryn L
KL
McAndrew
Magee Women's Research Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, U.S.A.
Kenneth
K
Marks
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D002945:Cisplatin
Cisplatin; SCLC; drug resistance