Lymphangiogenesis in gastric cancer regulated through Akt/mTOR-VEGF-C/VEGF-D axis.
Lymphangiogenesis in gastric cancer regulated through Akt/mTOR-VEGF-C/VEGF-D axis.
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DOI：
10.1186/s12885-015-1109-0
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发表时间：
2015-03-07
期刊：
影响因子：
3.8
通讯作者：
Chen C
中科院分区：
文献类型：
--
作者：
Chen H;Guan R;Lei Y;Chen J;Ge Q;Zhang X;Dou R;Chen H;Liu H;Qi X;Zhou X;Chen C
淋巴管生成在胃癌的转移和复发中起着重要作用。目前尚未见针对Akt/mTOR通路调控VEGF通路及胃癌淋巴管生成的报道。本研究旨在论证Akt/mTOR通路与胃癌中VEGF-C/-D的关系。我们从 55 名同意的患者身上收集了手术切除的胃腺癌标本。 p-Akt、p-mTOR、VEGF-C、VEGF-D 的免疫组织化学染色由两名独立病理学家进行并评分。结果以染色强度和阳性染色细胞率表示。我们还通过 D2-40 染色测量了淋巴管密度 (LVD)。在体外对胃癌细胞系SGC-7901给予不同剂量的p-Akt抑制剂LY294002（12.5μM、25μM、50μM）和p-mTOR抑制剂雷帕霉素（25nM、50nM、100nM）。分别采用MTT法检测24 h、48 h、72 h细胞生长抑制率，Western blot检测Akt、p-Akt、mTOR、p-mTOR、VEGF-C、VEGF-D蛋白表达。 55例胃癌临床标本中p-Akt、p-mTOR、VEGF-C和VEGF-D的阳性染色率分别为74.54%、85.45%、72.73%和58.18%。 p-Akt 和 p-mTOR 与 VEGF-C 和 VEGF-D 呈正相关（p<<0.01）。 LVD随着p-Akt、p-mTOR、VEGF-C和VEGF-D染色强度的增加而增加。 LY294002或雷帕霉素显着抑制SGC-7901细胞生长，且抑制率呈剂量和时间依赖性(p<0.001)。此外，p-Akt和p-mTOR的蛋白表达量与VEGF-C和VEGF-D的蛋白表达量呈正相关（p<0.05）。胃癌标本中LVD水平显着高于正常胃组织，且与p-Akt、p-mTOR、VEGF-C、VEGF-D呈正相关。体外抑制 p-Akt 和 p-mTOR 可显着降低肿瘤细胞 VEGF-C 和 VEGF-D。因此，我们推测胃癌的淋巴管生成可能与Akt/mTOR-VEGF-C/VEGF-D轴有关。
Lymphangiogenesis plays a significant role in metastasis and recurrence of gastric cancer. There is no report yet focusing on the modulation of VEGF pathway and lymphangiogenesis of gastric cancer by targeting Akt/mTOR pathway. This study aims to demonstrate the relationship between Akt/mTOR pathway and VEGF-C/-D in gastric cancer. We collected surgically resected gastric adenocarcinoma specimens from 55 consented patients. Immunohistochemistry staining of p-Akt, p-mTOR, VEGF-C, VEGF-D were performed and scored by two independent pathologists. The results were presented as staining intensity and positive staining cell rate. We also measured lymphatic vessel density (LVD) by D2-40 staining. Different dosages of p-Akt inhibitor LY294002 (12.5 μM, 25 μM, 50 μM) and p-mTOR inhibitor Rapamycin (25 nM, 50 nM, 100 nM) were given to gastric cancer cell line SGC-7901 in vitro. The inhibition rate of cell growth was tested by MTT at 24 h, 48 h and 72 h, respectively and protein expressions of Akt, p-Akt, mTOR, p-mTOR, VEGF-C and VEGF-D were examined by Western blot. The positive staining rates of p-Akt, p-mTOR, VEGF-C and VEGF-D in 55 gastric cancer clinical specimens were 74.54%, 85.45%, 72.73% and 58.18%. p-Akt and p-mTOR were positively correlated with VEGF-C and VEGF-D (p < 0.01). The LVD increased with incremental tendency of staining intensity of p-Akt, p-mTOR, VEGF-C and VEGF-D. LY294002 or Rapamycin significantly suppressed SGC-7901 cell growth and the inhibition rate was dose and time dependent (p < 0.001). In addition, the protein expression of p-Akt and p-mTOR were positively correlated with that of VEGF-C and VEGF-D (p < 0.05). The level of LVD in gastric cancer specimens was significant higher than that of normal gastric tissue and was positively correlated with p-Akt, p-mTOR, VEGF-C and VEGF-D. Inhibition of p-Akt and p-mTOR, in vitro, decreased tumor cell VEGF-C and VEGF-D significantly. Therefore, we concluded that lymphangiogenesis of gastric cancer might be related to Akt/mTOR-VEGF-C/VEGF-D axis.
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影响因子：
3.8
作者：
Shin JY;Kim JO;Lee SK;Chae HS;Kang JH
通讯作者：
Kang JH
影响因子：
7.4
作者：
Murakami, Daiki;Tsujitani, Shunichi;Ikeguchi, Masahide
通讯作者：
Ikeguchi, Masahide
磷酸化的AKT和MAPK表达在原发性肿瘤以及接受伊立替康 - 盘妥昔单抗的结直肠癌患者中的相应转移和临床结果中。
影响因子：
7.4
作者：
Scartozzi M;Giampieri R;Maccaroni E;Mandolesi A;Biagetti S;Alfonsi S;Giustini L;Loretelli C;Faloppi L;Bittoni A;Bianconi M;Del Prete M;Bearzi I;Cascinu S
通讯作者：
Cascinu S
影响因子：
3.7
作者：
Xu W;Huang JJ;Cheung PC
通讯作者：
Cheung PC
胃腺癌中蛋白激酶 B 磷酸化与血管内皮生长因子 A 和微血管密度相关
影响因子：
1.6
作者：
Zhou, X. D.;Chen, H. X.;Lv, N. H.
通讯作者：
Lv, N. H.