The molecular mechanism of luteolin-induced apoptosis is potentially related to inhibition of angiogenesis in human pancreatic carcinoma cells
The molecular mechanism of luteolin-induced apoptosis is potentially related to inhibition of angiogenesis in human pancreatic carcinoma cells
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DOI：
10.3892/or.2012.1914
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发表时间：
2012-10-01
期刊：
影响因子：
4.2
通讯作者：
Cao, Peng
中科院分区：
文献类型：
--
作者：
Cai, Xueting;Lu, Wuguang;Cao, Peng
木犀草素已被证明通过程序性细胞死亡（细胞凋亡）对各种癌症模型具有强大的抗癌作用。然而，这些影响的基本机制仍不清楚。在本研究中，我们研究了木犀草素是否可以通过细胞凋亡抑制胰腺癌细胞的增殖。我们在研究中使用了三种人胰腺癌细胞系：PANC-1、CoLo-357 和 BxPC-3。在木犀草素处理的胰腺癌细胞中，观察到细胞凋亡的典型特征。木犀草素处理 24 小时后，增加了促凋亡蛋白 Bax 的表达，降低了抗凋亡蛋白 Bcl-2 的表达，同时 caspase-3 和裂解 PARP 的水平也随之增加。木犀草素在体内抑制 CAM 中的 HUVEC 增殖和血管生长。此外，人胰腺癌细胞条件培养基中 VEGF 的浓度被木犀草素下调。通过共培养系统分析，用木犀草素预处理的胰腺癌细胞可以减少 HUVEC 毛细血管样结构的形成。 VEGF分泌的减少与抑制VEGF mRNA表达有关，其可能是通过抑制核转录因子NF-κB的转录活性来调节的。
Luteolin has been shown to have a strong anticancer effect on various cancer models via programmed cell death (apoptosis). However, the fundamental mechanisms of these effects are still unclear. In the present study, we examined the question of whether or not luteolin can inhibit proliferation of pancreatic carcinoma cells, via apoptosis. We used three human pancreatic carcinoma cell lines, PANC-1, CoLo-357 and BxPC-3 in our study. In luteolin-treated pancreatic carcinoma cells, typical features of apoptosis were observed. Luteolin increased the expression of the pro-apoptotic protein Bax and decreased the expression of the anti-apoptotic protein Bcl-2, with a concomitant increase in the levels of caspase-3 and cleaved PARP after treatment for 24 h. Luteolin inhibited HUVEC proliferation and vessel growth in CAM in vivo. In addition, the concentration of VEGF in the conditioned medium from human pancreatic carcinoma cells was downregulated by luteolin. Pancreatic carcinoma cells, pretreated with luteolin, could decrease the capillary-like structure formation by HUVEC, which was analyzed by a co-culture system. The abatement of VEGF secretion was related to the inhibition of VEGF mRNA expression, which may be regulated by inhibiting the transcription activity of nuclear transcription factor NF-kappa B.