Sex-dependent effects of estrogen pellets in human liver cancer xenograft models.

Liver cancer shows noticeable differences in the incidence rate and mortality between genders. To investigate the estrogen effect on tumor progression in liver cancer, we developed a xenograft model using estrogen pellets. SK-Hep1 cells (human male liver carcinoma) were inoculated into male or female nude mice. Subsequently, estrogen pellets were subcutaneously implanted into these xenograft models. Interestingly, the marked adverse effect of estrogen pellets (0.5 mg/21 days) were observed in the male-derived xenograft model, with increased ulcerative dermatitis in male mice than in female mice. Additionally, necrosis was observed in male mice with SK-Hep1-derived tumors. However, the estrogen pellet (0.5 mg/60 days) did not exhibit these adverse effects. Tumor growth in female mice was significantly suppressed by estrogen (0.5 mg/60 days). Tumor growth was also suppressed in male mice implanted with estrogen (0.5 mg/60 days), but the suppression was not significant. We found that estrogen-induced skin damage was more severe in male mice than female mice. The tumor suppression of estrogen was effective in female mice compared to male mice bearing liver cancer. The results suggest that the sex difference affects estrogen activity and thus should be considered in the preclinical assessment. © Korean Society of Toxicology 2019.