Effects of α-adrenoreceptor antagonists on apoptosis and proliferation of pancreatic cancer cells in vitro

AIM: To discuss the expression of alpha-adrenoreceptors in pancreatic cancer cell lines PC-2 and PC-3 and the effects of alpha 1- and alpha 2-adrenoreceptor antagonists, yohimbine and urapidil hydrochloride, on the cell lines in vitro. METHODS: We cultured the human ductal pancreatic adenocarcinoma cell lines PC-2 and PC-3 and analyzed the mRNA expression of alpha 1- and alpha 2-adrenergic receptors by reverse transcription polymerase chain reaction (RT-PCR). The effects of yohimbine and urapidil hydrochloride on cell proliferation were assessed by 3-(4,5-dimethylthiasol-2-yl)2,4,-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected using the terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling (TUNEL) assay and flow cytometry (FCM). RESULTS: PC-2 expressed mRNA in alpha 1- and alpha 2-adrenoreceptors. MTT assays showed that urapidil hydrochloride had no effect on PC-3 cell lines. However, exposure to urapidil hydrochloride increased DNA synthesis in PC-2 cell lines as compared to the control group. PC-2 cell lines were sensitive to both drugs. The proliferation of the 2 cell lines was inhibited by yohimbine. Cell proliferation was inhibited by yohimbine via apoptosis induction. CONCLUSION: The expression of alpha 1- and alpha 2-adrenoreceptors; is different in PC-2 and PC-3 cell lines, which might be indicative of their different functions. The alpha 2-adrenoceptor antagonist, yohimbine, can inhibit the proliferation of both cell lines and induce their apoptosis, suggesting that yohimbine can be used as an anticancer drug for apoptosis of PC-2 and PC-3 cells. (c) 2008 WJG. All rights reserved.