A Chinese herbal formula, Yi-Qi-Fu-Sheng, inhibits migration/invasion of colorectal cancer by down-regulating MMP-2/9 via inhibiting the activation of ERK/MAPK signaling pathways.
A Chinese herbal formula, Yi-Qi-Fu-Sheng, inhibits migration/invasion of colorectal cancer by down-regulating MMP-2/9 via inhibiting the activation of ERK/MAPK signaling pathways.
复制标题
益气扶生中药配方通过抑制 ERK/MAPK 信号通路的激活，下调 MMP-2/9 来抑制结直肠癌的迁移/侵袭。
DOI：
10.1186/1472-6882-13-65
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发表时间：
2013-03-18
影响因子：
--
通讯作者：
Lv S
中科院分区：
文献类型：
--
作者：
Deng W;Sui H;Wang Q;He N;Duan C;Han L;Li Q;Lu M;Lv S
益气复生方是一种中药方剂，临床上长期以来一直用于治疗癌症患者。我们的目的是确定其作为结直肠癌治疗方法的有效性。我们研究了YQFS对结直肠癌的治疗作用，以及潜在的机制，这是以前没有探索过的。首先，YQFS提取和化学表征。采用MTT法和transwell迁移实验检测YQFS对体外培养细胞增殖和迁移的影响。通过接种HCT-116细胞建立小鼠结肠直肠癌异种移植模型，小鼠接受三种口服剂量（200、400和800 mg/kg/天）中的一种以评价YQFS提取物的作用。明胶酶谱法检测MMP-2/9的表达。采用流式细胞术（FCM）检测细胞凋亡，TUNEL法检测细胞凋亡。在体外通过蛋白质印迹分析ERK和p-ERK的表达，在体内通过定量RT-PCR在mRNA水平评估ERK和p-ERK表达。我们的研究结果表明，YQFS显着抑制大肠癌细胞增殖，并诱导HCT-116细胞凋亡和细胞周期阻滞在G1-和S期。此外，YQFS通过抑制金属蛋白酶-2/9（MMP-2/9）的表达，在体外和体内有效地延缓肿瘤细胞的迁移和侵袭。此外，YQFS在体内对肿瘤生长具有抑制作用，并通过抑制ERK 1/2通路诱导细胞凋亡。这些结果表明，YQFS提取物具有抗结直肠癌的作用，这可能归因于ERK 1/2依赖性抑制MMP-2/9的表达。
A Chinese herbal formula, Yi-Qi-Fu-Sheng (YQFS), has long been employed clinically to treat cancer patients. We aimed to determine its effectiveness as a treatment method for colorectal cancer. We investigated the therapeutic effects of YQFS on colorectal cancer, as well as the underlying mechanisms, which have not previously been explored. First, YQFS was extracted and chemically characterized. We then tested the effects of YQFS on proliferation and migration by MTT and transwell migration assays in vitro. Mouse xenograft models of colorectal cancer were established by inoculation with HCT-116 cells, and mice received one of three oral doses (200, 400 and 800 mg/kg/day) to evaluate the effects of YQFS extract. Metalloproteinase-2/9 (MMP-2/9) expression in mice was evaluated by gelatin zymography assay. Apoptosis was evaluated by flow cytometry (FCM) analysis in vitro and by TUNEL assay in vivo. ERK and p-ERK expression were evaluated by western blot analysis at the protein level in vitro, and by quantitative RT-PCR at mRNA level in vivo. Our results show that YQFS significantly inhibits colorectal cancer cell proliferation and induces apoptosis and cell cycle arrest at the G1− and S-phase in HCT-116 cells. Furthermore, YQFS effectively retards tumor cell migration and invasion by inhibiting metalloproteinase-2/9 (MMP-2/9) expression, both in vitro and in vivo. Moreover, YQFS had an inhibitory effect on tumor growth in vivo, and induced apoptosis through the inhibition of the ERK1/2 pathway both in vitro and in vivo. These findings demonstrate that YQFS extract has an anti-tumor effect in colorectal cancer, which could be attributed to ERK1/2-dependent inhibition of MMP-2/9 expression.
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影响因子：
5.7
作者：
Kolinsky, Kenneth;Shen, Ben-Quan;Higgins, Brian
通讯作者：
Higgins, Brian
DOI：
10.3736/jcim20081203
发表时间：
2008-12-01
期刊：
Zhong xi yi jie he xue bao = Journal of Chinese integrative medicine
影响因子：
--
作者：
Sun, Zhen;Su, Yong-hua;Yue, Xiao-qiang
通讯作者：
Yue, Xiao-qiang
影响因子：
3.6
作者：
Marchbank, Tania;Ojobo, Ehighale;Playford, Raymond J.
通讯作者：
Playford, Raymond J.
影响因子：
7.9
作者：
Zhao, F. -R.;Mao, H-P;Gao, X. -M.
通讯作者：
Gao, X. -M.
影响因子：
5.4
作者：
Chen, Jiun-Yu;Chen, Hsiao-Ling;Chen, Chuan-Mu
通讯作者：
Chen, Chuan-Mu