The effect of mitotane on viability, steroidogenesis and gene expression in NCI‑H295R adrenocortical cells

摘要: Mitotane, also known as o,p'‑DDD or (RS)‑1‑chl-oro‑2‑[2,2‑dichloro‑1‑(4‑chlorophenyl)‑ethyl]‑benzene, is an adrenal cortex-specific cytotoxic drug used in the therapy of adrenocortical carcinoma (ACC). The inhibits steroidogenesis, however, mechanisms its anticancer and antisteroidogenic effects remain unknown. At present, data on impact mitotane cell viability regulation genes encoding proteins associated with steroids synthesis cortex, including cortisol dehydroepiandrosterone sulfate (DHEAS), are limited contradictory. In present study, effect 24‑h treatment ACC line, NCI‑H295R, was analyzed, identifying a decrease increase caspase‑3 ‑7 activities. Mitotane led to decreased DHEAS concentration culture media. Concomitantly, resulted mRNA levels two cytochromes P450 (CYP11A1 CYP17A1), mRNAs involved DHEAS. did not affect cyclin dependent kinase inhibitor 1A (encoding p21) MYC cMyc). cMyc p21 key transcription factors cycle regulation. However, inhibited expression transforming growth factor β1 gene, potent proliferation steroidogenesis. PRKAR1A, protein A regulatory subunit, activation PRKAR1A were reduced following mitotane. Results indicate that markedly secretion Reduced TGFB1 cannot account fully for CYP11A1 CYP17A1. We hypothesized NCI‑H295R cells presence may be result apoptosis triggered by increased Since stable mitotane, mechanism which induced remains