Sungryong Oh1, Joohee Jung2. 1. College of Pharmacy, Duksung Women's University, #33, Samyang-ro 144-gil, Dobong-gu, Seoul, 01369, South Korea. 2. College of Pharmacy, Duksung Women's University, #33, Samyang-ro 144-gil, Dobong-gu, Seoul, 01369, South Korea. joohee@duksung.ac.kr.
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.
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.
Entities:
Keywords:
Cardiotoxicity; Doxorubicin; Liver cancer; Sex difference; The Korea Institute of Drug Safety & risk management database; Xenograft model
Authors: Wanjuan Yang; Jorge Soares; Patricia Greninger; Elena J Edelman; Howard Lightfoot; Simon Forbes; Nidhi Bindal; Dave Beare; James A Smith; I Richard Thompson; Sridhar Ramaswamy; P Andrew Futreal; Daniel A Haber; Michael R Stratton; Cyril Benes; Ultan McDermott; Mathew J Garnett Journal: Nucleic Acids Res Date: 2012-11-23 Impact factor: 16.971