首页> 外文期刊>Current therapeutic research, clinical and experimental. >Effects of Lorglumide on Growth and Invasion of Human Pancreatic Cancer Cell Line Mia PaCa-2 In Vitro Through the Cholecystokinin-Cholecystokinin-1 Receptor Pathway
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Effects of Lorglumide on Growth and Invasion of Human Pancreatic Cancer Cell Line Mia PaCa-2 In Vitro Through the Cholecystokinin-Cholecystokinin-1 Receptor Pathway

机译:Lorglumide通过胆囊收缩素-胆囊收缩素-1受体途径对人胰腺癌细胞系Mia PaCa-2生长和侵袭的影响

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BACKGROUND! Cholecystokinin (CCK) has been found to be a growth stimulant through its special receptor pathway, especially for gastrointestinal malignancies. Although the CCK-1 receptor has been shown to be highly expressed in resected human pancreatic cancer samples, its role is less clear.OBJECTIVE: The aim of this in vitro study was to investigate the CCK-1 receptor expression and the function of the CCK-CCK-1 receptor pathway in the human pancreatic adenocarcinoma cell line, Mia PaCa-2.METHODS! The expression of the CCK-1 receptor in Mia PaCa-2 cells was detected by reverse-transcriptase polymerase chain reaction and flow cytometry. CCK-1 receptor agonist CCK-8S (the major transmitter form of CCK) and antagonist lorglumide were cultured respectively with Mia PaCa-2. Three groups were created for this study: CCK-8S group (Mia PaCa-2 cells treated with CCK-8S), lorglumide group (Mia PaCa-2 cells treated with lorglumide), and the control group (Mia PaCa-2 cells alone). Investigators were blinded to group designation. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolmm bromide (MTT) and flow cytometry were used to detect the cell growth, cell cycle, and apoptosis. Apoptosis index rate was measured by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling. Cell invasion ability was observed by invasion assay. Expression of matrix metalloproteinase-2 (MMP-2) was measured by Western blotting.RESULTS: Mia PaCa-2 cells were found to express the CCK-1 receptor. Compared with the control group (70.2% [1.5%]), CCK-8S was associated with significant mean (SD) cell proliferation (85.1% {1-7%}; P = 0.039), and the ratio in the S stage of the cell cycle increased significantly (50.5% [1.7%] vs 42.2% [1-4%}; P = 0.021). CCK-8S was also associated with increased Mia PaCa-2 cell invasion ability (123.8 [1.7] vs 102.1 [5.8]; P = 0.005 vs control). Compared with the control group, lorglumide was associated with significantly inhibited cell growth (52.1% [1.8%]; P = 0.002) and cell invasion (77.6% [1.2%]; P = 0.003). Lorglumide also induced G0/G1 cell cycle arrest and apoptosis (27.1% [3.5%] vs 3.7% [0.6%]; P = 0.003 vs control). The change of invasion ability appeared to be mediated by MMP-2 expression, which was upregu-lated by CCK-8S and downregulated by lorglumide.CONCLUSION: The findings of this in vitro study suggest that CCK may exert a trophic action on the Mia PaCa-2 cell line, while lorglumide inhibited the cell growth and invasion.
机译:背景!胆囊收缩素(CCK)已通过其特殊的受体途径成为一种生长刺激剂,特别是对于胃肠道恶性肿瘤。尽管已显示CCK-1受体在切除的人胰腺癌样品中高表达,但其作用尚不清楚。目的:本体外研究的目的是研究CCK-1受体的表达及其功能-CCK-1受体通路在人胰腺腺癌细胞系Mia PaCa-2.METHODS!通过逆转录酶聚合酶链反应和流式细胞仪检测Mia PaCa-2细胞中CCK-1受体的表达。用Mia PaCa-2分别培养CCK-1受体激动剂CCK-8S(CCK的主要递质形式)和拮抗剂洛格鲁胺。为该研究创建了三组:CCK-8S组(用CCK-8S处理的Mia PaCa-2细胞),lorglumide组(用lorglumide处理的Mia PaCa-2细胞)和对照组(仅Mia PaCa-2细胞) 。研究人员对小组指定不知情。使用3- [4,5-二甲基噻唑-2-基] -2,5-二苯基四唑毫米溴化物(MTT)和流式细胞仪检测细胞的生长,细胞周期和凋亡。通过末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记来测量细胞凋亡指数。通过侵袭测定观察细胞侵袭能力。结果:Mia PaCa-2细胞表达CCK-1受体,Western blotting检测基质金属蛋白酶-2(MMP-2)的表达。与对照组相比(70.2%[1.5%]),CCK-8S与平均(SD)细胞增殖显着相关(85.1%{1-7%}; P = 0.039),并且在S期的比例细胞周期显着增加(50.5%[1.7%]对42.2%[1-4%}; P = 0.021)。 CCK-8S也与增加的Mia PaCa-2细胞侵袭能力有关(123.8 [1.7]对102.1 [5.8]; P = 0.005对对照)。与对照组相比,洛格鲁胺与细胞生长受到显着抑制(52.1%[1.8%]; P = 0.002)和细胞浸润(77.6%[1.2%]; P = 0.003)相关。洛格鲁米德还诱导G0 / G1细胞周期阻滞和凋亡(27.1%[3.5%]对3.7%[0.6%]; P = 0.003对对照)。侵袭能力的改变似乎是由MMP-2表达介导的,其受CCK-8S上调并受洛格鲁米德下调。结论:体外研究的结果提示CCK可能对Mia PaCa发挥营养作用。 -2细胞系,而洛美糖胺抑制细胞生长和侵袭。

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