Search

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., (Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background/aim: Our earlier studies on ovarian tumor xenografts provide evidence that co-treatment with selenite prevents the development of resistance to single-treatment using the drug cisplatin. However, these studies did not reflect the repetitive schedule of clinical chemotherapy. We hypothesized that selenite can enhance the effectiveness of cisplatin during the course of repeated treatments, reflecting clinical practices., Materials and Methods: Multiple i.p. injections of cisplatin (5.2 mg/kg) alone, or with selenite (1.5 mg/kg), were administered to mice bearing subcutaneous xenografts of human ovarian tumor (A2780) cells and the tumor volume was recorded., Results: Selenite increased and prolonged the efficacy of multiple cisplatin treatments, although selenite was not an effective inhibitor by itself. In the absence of selenite, the effectiveness of cisplatin decreased., Conclusion: The ability of selenite to prolong the effectiveness of repetitive cisplatin treatment, most likely by preventing the development of resistance, makes it a strong candidate for inclusion in clinical trials.