百里醌抑制人胰腺癌BxPC-3细胞体外运动和侵袭的研究

Thymoquinone Inhibits Migration and Invasion of Human Pancreatic Cancer BxPC-3 Cells in vitro

背景:胰腺癌是恶性程度最高的消化道肿瘤,目前吉西他滨依赖的化疗对抑制胰腺癌转移的治疗效果欠佳。研究发现百里醌对多种肿瘤细胞具有抑制增殖、促进凋亡的作用。目的:探讨百里醌对人胰腺癌BxP C-3细胞体外运动和侵袭的影响及其作用机制。方法:常规培养人胰腺癌细胞株BxP C-3,加入不同浓度百里醌进行处理。采用Boyden小室法检测细胞体外运动、侵袭情况;蛋白质印迹法检测细胞FAK、Akt蛋白表达和Akt磷酸化水平的改变;免疫荧光技术检测细胞内FAK表达、细胞黏着斑和F-actin的变化。结果:10、25μmol/L百里醌对BxP C-3细胞体外运动的抑制率分别为43.4%、73.8%,对体外侵袭的抑制率分别为60.5%、75.6%,百里醌呈浓度依赖性地抑制胰腺癌BxP C-3细胞的体外运动、侵袭(P<0.05)。百里醌能明显下调BxP C-3细胞FAK表达,并抑制细胞磷酸化Akt的激活。百里醌可诱导FAK弥散分布于胞质,明显抑制黏着斑形成和F-actin的聚合集化。结论:百里醌通过抑制FAK/PI3K/Akt通路的信号转导和激酶活性,浓度依赖性地抑制人胰腺癌BxP C-3细胞的体外运动和侵袭。

BacKground:Human pancreatic cancer is a highIy maIignant tumor of digestive system. CurrentIy,gemcitabine based conventionaI chemotherapy has onIy very Iimited efficacy on metastasis of pancreatic cancer. Studies have shown that thymoquinone has remarkabIe effect of inhibiting proIiferation and enhancing apoptosis on a variety of cancer ceIIs. Aims:To investigate the effect and mechanism of thymoquinone on inhibiting the migration and invasion of human pancreatic cancer BxPC-3 ceIIs in vitro. Methods:Human pancreatic cancer BxPC-3 ceIIs were conventionaIIy cuItured and treated with different concentrations of thymoquinone. The migration and invasion of BxPC-3 ceIIs were determined by Boyden chamber assay. The expressions of FAK,Akt and phosphoryIation of Akt were measured by Western bIotting,and immunofIuorescence was used to detect expression of FAK,focaI adhesions and F-actin. Results:The inhibitory rates of 10,25μmoI/L thymoquinone on migration of BxPC-3 ceIIs were 43. 4% and 73. 8%,respectiveIy,and the inhibitory rates of invasion were 60. 5% and 75. 6%,respectiveIy. The reduction of migration and invasion of pancreatic cancer BxPC-3 ceIIs by thymoquinone was in a dose-dependent manner( P < 0. 05 ). Thymoquinone obviousIy down-reguIated the expression of FAK and suppressed the phosphoryIation of Akt in BxPC-3 ceIIs. Thymoquinone induced the dispersed distribution of FAK in cytopIasm and inhibited the formation of focaI adhesions and assembIy of F-actin. Conclusions:Thymoquinone inhibits the migration and invasion of human pancreatic cancer BxPC-3 ceIIs in a dose-dependent manner in vitro through suppression of FAK/PI3K/Akt signaIing pathway and activity of kinase.