Toxicology research · 2020
The intervention of valproic acid on the tumorigenesis induced by an environmental carcinogen of PAHs.
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Peng Junxuan, Cai Zuchao, Zhao Ruixue, Chen Jiahao, Liu Guochao, Dong Chao, Lim David, Feng Zhihui
Аннотация
This study investigated whether valproic acid (VPA, a histone deacetylase inhibitor) can interfere with the carcinogenicity of polycyclic aromatic hydrocarbons (PAHs). A typical representative compound of PAHs, 7,12-Dimethylbenz[a]anthracene (DMBA), was used to induce rat breast cancer. The results showed that therapeutic concentration of VPA (50 and 100 mg/kg) delayed the occurrence of tumors, reduced tumor formation rate and attenuated tumors growth, and have a protective effect on normal tissues. The macrophage-mediated inflammatory response was found to be associated with the observed effect of VPA. In addition, we screened and validated a possible gene, Sema3c, which was involved in DMBA-induced breast cancer development and can be inhibited by VPA.