Oh Sungryong, Jung Joohee
College of Pharmacy, Duksung Women's University, #33, Samyang-ro 144-gil, Dobong-gu, Seoul, 01369, South Korea.
Lab Anim Res. 2021 Feb 25;37(1):10. doi: 10.1186/s42826-021-00087-z.
The incidence and mortality of liver cancer show a great difference between the sexes. We established sex-dependent liver cancer xenograft models and investigated whether such sex-dependent models could be used to simultaneously evaluate the therapeutic and adverse effects of anticancer drugs for drug screening.
In the in-vitro test, the cytotoxicity of anticancer drugs (cisplatin, 5-fluorouracil, and doxorubicin) was compared between male- and female-derived liver cancer cell lines. Cisplatin and 5-fluorouracil exhibited cytotoxicity without sex-difference, but doxorubicin showed dose-dependently significant cytotoxicity only in male-derived cells. Our results showed a strong correlation between preclinical and clinical data with the use of sex-dependent liver cancer xenograft models. Moreover, the male-derived Hep3B-derived xenograft model was more sensitive than the female-derived SNU-387-derived xenograft model against doxorubicin treatment. Doxorubicin showed more severe cardiotoxicity in the male xenograft model than in the female model. We investigated the occurrence frequency of doxorubicin-related cardiotoxicity using data obtained from the Korea Institute of Drug Safety & Risk Management Database, but no significant difference was observed between the sexes.
Our results suggest that sex-dependent xenograft models are useful tools for evaluating the therapeutic and adverse effects of anticancer drugs, because sex is an important consideration in drug development.
肝癌的发病率和死亡率在性别上存在很大差异。我们建立了性别依赖性肝癌异种移植模型，并研究这种性别依赖性模型是否可用于同时评估抗癌药物的治疗效果和不良反应，以进行药物筛选。
在体外试验中，比较了源自雄性和雌性的肝癌细胞系对抗癌药物（顺铂、5-氟尿嘧啶和阿霉素）的细胞毒性。顺铂和5-氟尿嘧啶表现出无性别差异的细胞毒性，但阿霉素仅在源自雄性的细胞中表现出剂量依赖性的显著细胞毒性。我们的结果表明，使用性别依赖性肝癌异种移植模型时，临床前和临床数据之间存在很强的相关性。此外，源自雄性的Hep3B异种移植模型比源自雌性的SNU-387异种移植模型对阿霉素治疗更敏感。阿霉素在雄性异种移植模型中比在雌性模型中表现出更严重的心脏毒性。我们使用从韩国药物安全与风险管理研究所数据库获得的数据调查了阿霉素相关心脏毒性的发生频率，但未观察到性别之间的显著差异。
我们的结果表明，性别依赖性异种移植模型是评估抗癌药物治疗效果和不良反应的有用工具，因为性别是药物开发中的一个重要考虑因素。
