Effects of alpha-adrenoreceptor antagonists on apoptosis and proliferation of pancreatic cancer cells in vitro.
OBJECTIVE
To discuss the expression of alpha-adrenoreceptors in pancreatic cancer cell lines PC-2 and PC-3 and the effects of alpha1- and alpha2-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 alpha1- and alpha2-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 alpha1- and alpha2-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.


CONCLUSIONS
The expression of alpha1- and alpha2-adrenoreceptors is different in PC-2 and PC-3 cell lines, which might be indicative of their different functions. The alpha2-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.
Shen
Su-Gang
SG
Department of Hepatobiliary and Pancreas Surgery, the First Affiliated Hospital, Medical College, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
Zhang
Dong
D
Hu
Heng-Tong
HT
Li
Jun-Hui
JH
Wang
Zheng
Z
Ma
Qing-Yong
QY
D058668:Adrenergic alpha-1 Receptor Antagonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020287:In Situ Nick-End Labeling; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010879:Piperazines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015016:Yohimbine / Q000494:pharmacology*
D058668:Adrenergic alpha-1 Receptor Antagonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000970:Antineoplastic Agents; D010879:Piperazines; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; C015568:urapidil