Sex dimorphism in antitumor response of chemotherapeutic drug cisplatin in a murine host-bearing a T-cell lymphoma

Abstract

Previously we have demonstrated that in-vivo growth of a murine T-cell lymphoma of spontaneous origin designated as Dalton's lymphoma (DL) shows sex dimorphism (J Rep Immunol 2005; 65:17-32). It remained unclear, however, if DL growth in female and male tumor-bearing hosts also shows a sex-dependent differential susceptibility to the antitumor action of cancer chemotherapeutic drugs. In this study we have demonstrated that in-vivo administration of anticancer drugs: cisplatin or doxorubicin to the DL-bearing host results in a sex-dependent different antitumor activity of the drugs, causing a sex dimorphism in the antitumor response of the drugs with respect to tumor growth inhibition. The antitumor effect of both drugs was found to be better in male tumor-bearing hosts compared with female tumor-bearing hosts. The study also shows that DL cells obtained from male and female tumor-bearing hosts display a differential growth response to following treatment with cisplatin in vitro. Cell growth regulatory proteins: interleukin-2, interferon-gamma, tumor growth factor-beta, p53, caspase-activated DNase, vascular endothelial growth factor, and interleukin-2 receptor were found to be involved in the observed sex-specific response of DL cells to the antitumor action of cisplatin. Moreover, gonadal hormones: androgen, estrogen, and their specific antagonists flutamide and tamoxifen were found to directly modulate the cytotoxicity of cisplatin against DL cells in vitro. This study, therefore, suggests for the first time that the efficacy of cancer chemotherapeutic may vary in a sex-specific manner in a host-bearing a T-cell lymphoma.