p38 MAP kinase inhibition promotes primary tumour growth via VEGF independent mechanism.
p38 MAP kinase inhibition promotes primary tumour growth via VEGF independent mechanism.
复制标题
DOI：
10.1186/1477-7819-7-89
复制
发表时间：
2009-11-15
影响因子：
3.2
通讯作者：
Redmond HP
中科院分区：
文献类型：
--
作者：
O'Sullivan AW;Wang JH;Redmond HP
手术损伤诱导炎症反应，激活P38 MAP激酶，实体肿瘤也可以释放细胞因子。因此，抑制这些途径可能会减少肿瘤生长。我们开始研究P38-MAPK抑制对体外细胞凋亡、增殖、VEGF释放和细胞周期效应的影响，以及对体内原发性肿瘤生长的影响。4T-1细胞（2 × 105个细胞/孔）与对照、25、50或100 ng/ml SB-202190在24孔板中孵育24小时。随后对细胞进行凋亡、增殖、VEGF释放和细胞周期分析。每只Balb-c小鼠腹腔皮下注射1 × 106个4T1细胞，然后随机分为对照组和腹腔注射SB202190 （2.5 μM/kg）。每隔一天测量肿瘤大小，第24天处死动物并评估血清VEGF。体外抑制P38-MAPK可显著降低细胞增殖（75.2±8.4%比100±4.3%,p < 0.05）和G1细胞周期期（35.9±1.1%比32.5±0.6%,p < 0.05），但细胞凋亡和VEGF水平无显著变化。在体内，P38-MAPK抑制导致原发肿瘤生长增加（155.6±34.9 mm3 vs 86.7±18.2 mm3, p < 0.05）。P38-MAPK抑制也降低了循环VEGF水平，但差异不显著（101.9±27.1 ηg/ml与158.6±27.1 ηg/ml相比）。这些研究结果表明，P38-MAPK体外抑制可减少细胞增殖和G1细胞周期，并促进体内原发性肿瘤生长。这些影响似乎与VEGF无关。
The surgical insult induces an inflammatory response that activates P38 MAP kinases and solid tumours can also release cytokines. Therfore inhibition of these pathways may reduce tumour growth We set out to examine the effects of P38-MAPK inhibition on apoptosis, proliferation, VEGF release and cell cycle effects in-vitro and on primary tumour growth in-vivo. 4T-1 cells (2 × 105cells/well) were incubated, in 24 well plates with control, 25, 50 or 100 ng/ml of SB-202190 for 24 hours. Cells were subsequently asessed for apoptosis, proliferation, VEGF release and cell cycle analysis. Balb-c mice each received 1 × 106 4T1 cells subcutaneously in the flank and were then randomised to receive control or SB202190 (2.5 μM/kg) by intraperitoneal injection daily. Tumour size was measured alternate days and at day 24 animals were sacrificed and serum VEGF assessed. P38-MAPK inhibition in-vitro resulted in a significant reduction in proliferation (75.2 ± 8.4% vs. 100 ± 4.3%, p < 0.05) and G1 cell cycle phase(35.9 ± 1.1% vs. 32.5 ± 0.6%, p < 0.05) but no significant changes in apoptosis or VEGF levels. In-vivo, P38-MAPK inhibition resulted in an increase in primary tumour growth (155.6 ± 34.9 vs. 86.7 ± 18.2 mm3, p < 0.05). P38-MAPK inhibition also lowered circulating VEGF levels but this difference was not significant (101.9 ± 27.1 ηg/ml compared to 158.6 ± 27.1 ηg/ml) These findings demonstrate that P38-MAPK inhibition in-vitro reduces proliferation and G1 cell cycle phase as well as promoting primary tumour growth in-vivo. These effects would appear to be independent of VEGF.
登录
查看更多内容
DOI：
10.1165/ajrcmb.26.5.4689
发表时间：
2002-05-01
影响因子：
6.4
作者：
Greenberg, AK;Basu, S;Lee, TC
通讯作者：
Lee, TC
影响因子：
2.2
作者：
O'Sullivan, Adrian W.;Wang, Jiang H.;Redmond, Henry P.
通讯作者：
Redmond, Henry P.
影响因子：
8
作者：
Hardwick, JCH;van den Brink, GR;Peppelenbosch, MP
通讯作者：
Peppelenbosch, MP
影响因子：
56.9
作者：
MANSOUR, SJ;MATTEN, WT;AHN, NG
通讯作者：
AHN, NG
DOI：
10.1006/bbrc.1995.2069
发表时间：
1995-07-26
影响因子：
3.1
作者：
ATTEN, MJ;ATTAR, BM;HOLIAN, O
通讯作者：
HOLIAN, O