Sex-dependent liver cancer xenograft models for predicting clinical data in the evaluation of anticancer drugs
10.1186/s42826-021-00087-z
- Author:
Sungryong OH
1
;
Joohee JUNG
Author Information
1. College of Pharmacy, Duksung Women’s University, #33, Samyang-ro 144-gil, Dobong-gu, Seoul, 01369, South Korea
- Publication Type:Research
- From:Laboratory Animal Research
2021;37(1):82-89
- CountryRepublic of Korea
- Language:English
-
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.
