Delphinidin reduces cell proliferation and induces apoptosis of non-small-cell lung cancer cells by targeting EGFR/VEGFR2 signaling pathways.
Delphinidin reduces cell proliferation and induces apoptosis of non-small-cell lung cancer cells by targeting EGFR/VEGFR2 signaling pathways.
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DOI：
10.1371/journal.pone.0077270
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Afaq F
中科院分区：
文献类型：
--
作者：
Pal HC;Sharma S;Strickland LR;Agarwal J;Athar M;Elmets CA;Afaq F
表皮生长因子受体（EGFR）和血管内皮生长因子受体2（VEGFR 2）已成为非小细胞肺癌（NSCLC）的两个有效临床靶点。在目前的研究中，我们发现，飞燕草素，花青素，存在于色素水果和蔬菜，是一种有效的抑制剂，EGFR和VEGFR 2在NSCLC细胞过度表达EGFR/VEGFR 2。使用这些细胞，我们接下来确定了飞燕草素对体外细胞生长和凋亡以及体内肿瘤生长和血管生成的影响。用Delphinidin（5-60 µM）处理NSCLC细胞可抑制PI 3 K的激活以及AKT和MAPKs的磷酸化。此外，用飞燕草素处理NSCLC细胞导致细胞生长的抑制，而对正常人支气管上皮细胞没有显著的毒性作用。具体而言，用飞燕草素（5-60 μM）处理NCI-H441和SK-MES-1细胞导致（i）PARP蛋白裂解，（ii）半胱天冬酶-3和-9活化，（iii）抗凋亡蛋白（Bcl 2、Bcl-xL和Mcl-1）下调，（iv）促凋亡蛋白（Bax和巴克）上调，以及（v）PCNA和细胞周期蛋白D1表达降低。此外，在皮下植入人NSCLC细胞的无胸腺裸鼠中，与对照小鼠相比，飞燕草苷处理引起（i）肿瘤生长的显著抑制，（ii）细胞增殖标记物（Ki 67和PCNA）和血管生成标记物（CD 31和VEGF）的表达降低，以及（iii）细胞凋亡的诱导。基于这些观察结果，我们建议，飞燕草素，单独或作为目前的治疗辅助，可用于非小细胞肺癌的管理，特别是那些过度表达EGFR和VEGFR 2。
Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor 2 (VEGFR2) have emerged as two effective clinical targets for non-small-cell lung cancer (NSCLC). In the present study, we found that delphinidin, an anthocyanidin, present in pigmented fruits and vegetables, is a potent inhibitor of both EGFR and VEGFR2 in NSCLC cells that overexpress EGFR/VEGFR2. Using these cells, we next determined the effects of delphinidin on cell growth and apoptosis in vitro and on tumor growth and angiogenesis in vivo. Delphinidin (5-60 µM) treatment of NSCLC cells inhibited the activation of PI3K, and phosphorylation of AKT and MAPKs. Additionally, treatment of NSCLC cells with delphinidin resulted in inhibition of cell growth without having significant toxic effects on normal human bronchial epithelial cells. Specifically, treatment of NCI-H441 and SK-MES-1 cells with delphindin (5-60 µM) resulted in (i) cleavage of PARP protein, (ii) activation of caspase-3 and -9, (iii) downregulation of anti-apoptotic proteins (Bcl2, Bcl-xL and Mcl-1), (iv) upregulation of pro-apoptotic proteins (Bax and Bak), and (v) decreased expression of PCNA and cyclin D1. Furthermore, in athymic nude mice subcutaneously implanted with human NSCLC cells, delphinidin treatment caused a (i) significant inhibition of tumor growth, (ii) decrease in the expression of markers for cell proliferation (Ki67 and PCNA) and angiogenesis (CD31 and VEGF), and (iii) induction of apoptosis, when compared with control mice. Based on these observations, we suggest that delphinidin, alone or as an adjuvant to current therapies, could be used for the management of NSCLC, especially those that overexpress EGFR and VEGFR2.
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表皮生长因子受体抑制通过血管正常化调节微环境，从而提高化疗和放疗疗效。
影响因子：
3.7
作者：
Cerniglia, George J.;Pore, Nabendu;Tsai, Jeff H.;Schultz, Susan;Mick, Rosemarie;Choe, Regine;Xing, Xiaoman;Durduran, Turgut;Yodh, Arjun G.;Evans, Sydney M.;Koch, Cameron J.;Hahn, Stephen M.;Quon, Harry;Sehgal, Chandra M.;Lee, William M. F.;Maity, Amit
通讯作者：
Maity, Amit
影响因子：
50.5
作者：
Ferrero, JM;Ramaioli, A;Milano, G
通讯作者：
Milano, G
影响因子：
5.5
作者：
Haseeb, Abdul;Chen, Dongxing;Haqqi, Tariq M.
通讯作者：
Haqqi, Tariq M.
影响因子：
28.2
作者：
Corcoran RB;Ebi H;Turke AB;Coffee EM;Nishino M;Cogdill AP;Brown RD;Della Pelle P;Dias-Santagata D;Hung KE;Flaherty KT;Piris A;Wargo JA;Settleman J;Mino-Kenudson M;Engelman JA
通讯作者：
Engelman JA
DOI：
10.1073/pnas.0905056106
发表时间：
2009-11-17
影响因子：
11.1
作者：
Faber, Anthony C.;Li, Danan;Engelman, Jeffrey A.
通讯作者：
Engelman, Jeffrey A.