Lab Anim Res.  2021 Mar;37(1):82-89. 10.1186/s42826-021-00087-z.

Sex-dependent liver cancer xenograft models for predicting clinical data in the evaluation of anticancer drugs

• Oh S
• Jung J

• KMID: 2514400
• DOI: http://doi.org/10.1186/s42826-021-00087-z

Abstract

Background
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.
Results
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.
Conclusions
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.

Keyword

Doxorubicin; Sex difference; Cardiotoxicity; Liver cancer; Xenograft model; The Korea Institute of Drug Safety & risk management database