Prevention of carboplatin-induced resistance in human ovarian tumor xenografts by selenite.

Background/aim: We have been exploring a prevention approach to the problem of drug resistance which develops during ovarian cancer chemotherapy. We have previously described an in vivo model of the development of resistance to the chemotherapy drug cisplatin in xenografts, and the prevention of this resistance by selenium compounds. However, a different platinum-based drug, carboplatin, is frequently utilized in ovarian cancer treatment. The aim of the present study was to design a model for the induction of resistance by carboplatin in vivo.

Materials And Methods: Tumors were initiated in immunodeficient mice by subcutaneous inoculation of A2780 human ovarian tumor cells. The sensitivity of the resulting tumors to therapy was determined by measuring the effect on tumor growth of a single intraperitoneal (i.p.) treatment with a high dose of carboplatin.

Results: The growth of control tumors was completely (although temporarily) stopped by this treatment; however, a single pre-treatment with a low i.p. dose of carboplatin resulted in the rapid development of resistance to carboplatin, and cross-resistance to cisplatin. Pre-treatment with selenite in addition to carboplatin prevented the induction of resistance. When cells from these pre-treated tumors were transplanted to new animals, the derivative tumors retained the sensitive or resistant phenotype of their tumor of origin.

Conclusion: Selenite can prevent the induction of resistance by carboplatin in human ovarian tumors, and thus may offer an approach to extending the long-term efficacy of platinum chemotherapy.