α-肾上腺素能受体拮抗剂对体外胰腺癌细胞凋亡和增殖的影响。
Effects of alpha-adrenoreceptor antagonists on apoptosis and proliferation of pancreatic cancer cells in vitro.
作者信息
Shen Su-Gang, Zhang Dong, Hu Heng-Tong, Li Jun-Hui, Wang Zheng, Ma Qing-Yong
机构信息
Department of Hepatobiliary and Pancreas Surgery, the First Affiliated Hospital, Medical College, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
出版信息
World J Gastroenterol. 2008 Apr 21;14(15):2358-63. doi: 10.3748/wjg.14.2358.
AIM
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.
CONCLUSION
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.
目的
探讨α-肾上腺素能受体在胰腺癌细胞系PC-2和PC-3中的表达，以及α1-和α2-肾上腺素能受体拮抗剂育亨宾和盐酸乌拉地尔对这些细胞系的体外作用。
方法
培养人胰腺导管腺癌细胞系PC-2和PC-3，采用逆转录聚合酶链反应（RT-PCR）分析α1-和α2-肾上腺素能受体的mRNA表达。通过3-(4,5-二甲基噻唑-2-基)-2,4-二苯基四氮唑溴盐（MTT）法评估育亨宾和盐酸乌拉地尔对细胞增殖的影响。使用末端脱氧核苷酸转移酶（TdT）介导的生物素-16-dUTP缺口末端标记（TUNEL）法和流式细胞术（FCM）检测细胞凋亡。
结果
PC-2表达α1-和α2-肾上腺素能受体的mRNA。MTT试验表明，盐酸乌拉地尔对PC-3细胞系无影响。然而，与对照组相比，盐酸乌拉地尔处理使PC-2细胞系中的DNA合成增加。PC-2细胞系对两种药物均敏感。育亨宾抑制这两种细胞系的增殖。育亨宾通过诱导凋亡抑制细胞增殖。
结论
PC-2和PC-3细胞系中α1-和α2-肾上腺素能受体的表达不同，这可能表明它们具有不同的功能。α2-肾上腺素能受体拮抗剂育亨宾可抑制两种细胞系的增殖并诱导其凋亡，提示育亨宾可作为PC-2和PC-3细胞凋亡的抗癌药物。
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