Proanthocyanidins Inhibit In vitro and In vivo Growth of Human Non-Small Cell Lung Cancer Cells by Inhibiting the Prostaglandin E2 and Prostaglandin E2 Receptors
Proanthocyanidins Inhibit In vitro and In vivo Growth of Human Non-Small Cell Lung Cancer Cells by Inhibiting the Prostaglandin E2 and Prostaglandin E2 Receptors
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DOI：
10.1158/1535-7163.mct-09-0638
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发表时间：
2010-03-01
影响因子：
5.7
通讯作者：
Katiyar, Santosh K.
中科院分区：
文献类型：
--
作者：
Sharma, Som D.;Meeran, Syed M.;Katiyar, Santosh K.
环氧合酶-2(COX-2)和前列腺素(PG)的过度表达与多种人类癌症有关。在此，我们研究了葡萄籽原花青素(GSP)对非小细胞肺癌(NSCLC)细胞的化疗作用是否通过抑制COX-2和PGE(2)/PGE(2)受体的表达而起作用。采用Western blotting、荧光激活细胞分选分析和逆转录聚合酶链式反应(RT-PCR)检测GSP对人NSCLC细胞增殖、凋亡及COX-2、PGE(2)和PGE(2)受体表达的影响。体外培养的非小细胞肺癌细胞(A549、H1299、H460、H226和H157)经GSPs处理后，细胞生长受到明显抑制，并诱导细胞发生凋亡，这与其抑制COX-2、PGE(2)和PGE(2)受体(EP1和EP4)的过表达有关。用PAN-COX抑制剂吲哚美辛处理细胞，或瞬时将COX-2小干扰RNA导入细胞，也会抑制细胞生长并诱导细胞死亡。此外，还观察了添加GSP的AIN76A对照饲料对荷瘤裸鼠移植瘤COX-2、PGE(2)和PGE(2)受体表达的影响。膳食GSP(0.5%，w/w)对NSCLC移植瘤的生长抑制作用与抑制肿瘤中的COX-2、PGE(2)和PGE(2)受体(EP1、EP3和EP4)有关。这项临床前研究证明，GSPs在体内外对肺癌细胞的化疗作用至少部分是通过抑制COX-2的表达，进而抑制PGE(2)和PGE(2)受体来实现的。摩尔癌症治疗；9(3)；569-80。(C)2010年AACR。
Overexpression of cyclooxygenase-2 (COX-2) and prostaglandins (PG) is linked to a wide variety of human cancers. Here, we assessed whether the chemotherapeutic effect of grape seed proanthocyanidins (GSP) on non-small cell lung cancer (NSCLC) cells is mediated through the inhibition of COX-2 and PGE(2)/PGE(2) receptor expression. The effects of GSPs on human NSCLC cell lines in terms of proliferation, apoptosis, and expression of COX-2, PGE(2), and PGE(2) receptors were determined using Western blotting, fluorescence-activated cell sorting analysis, and reverse transcription-PCR. In vitro treatment of NSCLC cells (A549, H1299, H460, H226, and H157) with GSPs resulted in significant growth inhibition and induction of apoptosis, which were associated with the inhibitory effects of GSPs on the overexpression of COX-2, PGE(2), and PGE(2) receptors (EP1 and EP4) in these cells. Treatment of cells with indomethacin, a pan-COX inhibitor, or transient transfection of cells with COX-2 small interfering RNA, also inhibited cell growth and induced cell death. The effects of a GSP-supplemented AIN76A control diet fed to nude mice bearing tumor xenografts on the expression of COX-2, PGE(2), and PGE(2) receptors in the xenografts were also evaluated. The growth-inhibitory effect of dietary GSPs (0.5%, w/w) on the NSCLC xenograft tumors was associated with the inhibition of COX-2, PGE(2), and PGE(2) receptors (EP1, EP3, and EP4) in tumors. This preclinical study provides evidence that the chemotherapeutic effect of GSPs on lung cancer cells in vitro and in vivo is mediated, at least in part, through the inhibition of COX-2 expression and subsequently the inhibition of PGE(2) and PGE(2) receptors. Mol Cancer Ther; 9(3); 569-80. (C) 2010 AACR.