Department of Pharmacology, Fujian Medical University, Fuzhou 350004, Fujian, China.
Pharmacol Rep. 2013;65(3):682-8. doi: 10.1016/s1734-1140(13)71046-6.
Pancreatic cancer treatment is limited and effective drugs are needed. We investigated cucurmosin (CUS)-induced apoptosis in cystic fibrosis pancreatic adenocarcinoma cells (CFPAC-1) and a possible mechanism of action to evaluate the clinical application potential of this new Type I ribosome-inactivating protein.
We analyzed the growth inhibition and apoptosis of CFPAC-1 cells via methylthiazol tetrazolium assay and fluorescence-activated cell sorting. Western blot was used to analyze the protein levels of caspase 3, bcl-2, caspase 9, platelet-derived growth factor receptor (PDGFR)-β, PI3K, Akt, p-Akt, the mammalian target of rapamycin (mTOR), p-mTOR, P70S6K-α, p-P70S6K-α, 4E-BP1, p-4E-BP1 and p-Bad after CUS intervention. The mRNA expression of PDGFR-β was analyzed using reverse transcription polymerase chain reaction.
CUS inhibited the proliferation of pancreatic cancer cells. The induction of apoptosis depended on the CUS dose and incubation time. The drug inhibited all of the examined proteins in the PI3K/Akt/mTOR signalling pathway and induced the active fragments of caspase 3 and caspase 9. CUS downregulated PDGFR-β expression but no significant change was observed at the mRNA level.
CUS strongly inhibits the growth of CFPAC-1 by inducing cell apoptosis. CUS downregulated the expression of PDGFR-β at the protein level and induced the apoptosis of CFPAC-1 through the PI3K/Akt/mTOR signalling pathway.
胰腺癌的治疗方法有限，需要有效的药物。我们研究了苦瓜素（CUS）在囊性纤维化胰腺腺癌细胞（CFPAC-1）中的诱导凋亡作用及其作用机制，以评估这种新型 I 型核糖体失活蛋白的临床应用潜力。
通过噻唑蓝（MTT）比色法和流式细胞术分析 CFPAC-1 细胞的生长抑制和凋亡情况。Western blot 分析 caspase 3、bcl-2、caspase 9、血小板衍生生长因子受体（PDGFR）-β、PI3K、Akt、p-Akt、哺乳动物雷帕霉素靶蛋白（mTOR）、p-mTOR、p70S6K-α、p-P70S6K-α、4E-BP1、p-4E-BP1 和 p-Bad 蛋白水平。逆转录聚合酶链反应（RT-PCR）分析 PDGFR-β 的 mRNA 表达。
CUS 抑制胰腺癌细胞的增殖。细胞凋亡的诱导取决于 CUS 剂量和孵育时间。该药物抑制了 PI3K/Akt/mTOR 信号通路中的所有检测蛋白，并诱导了 caspase 3 和 caspase 9 的活性片段。CUS 下调 PDGFR-β 的表达，但在 mRNA 水平上没有明显变化。
CUS 通过诱导细胞凋亡强烈抑制 CFPAC-1 的生长。CUS 在蛋白水平下调 PDGFR-β 的表达，并通过 PI3K/Akt/mTOR 信号通路诱导 CFPAC-1 的凋亡。
