Metformin inhibits the IL-6-induced epithelial-mesenchymal transition and lung adenocarcinoma growth and metastasis.
Metformin inhibits the IL-6-induced epithelial-mesenchymal transition and lung adenocarcinoma growth and metastasis.
复制标题
二甲双胍抑制 IL-6 诱导的上皮间质转化和肺腺癌生长和转移
DOI：
10.1371/journal.pone.0095884
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
He Y
中科院分区：
文献类型：
--
作者：
Zhao Z;Cheng X;Wang Y;Han R;Li L;Xiang T;He L;Long H;Zhu B;He Y
目的上皮间质转化（EMT）在肿瘤发生中起重要作用。然而，肺腺癌中EMT的潜在机制以及如何抑制这一过程仍有待探索。本研究探讨了IL-6在肺腺癌细胞EMT中的作用，并探讨了二甲双胍对这一过程的潜在影响。方法采用细胞侵袭实验和MTT法检测细胞的侵袭能力和增殖能力。采用Western blotting、免疫荧光、real-time PCR、ELISA和免疫组化方法检测IL-6、E-cadherin、Vimentin和p-STAT 3的表达。结果IL-6通过磷酸化STAT 3促进肺腺癌细胞EMT侵袭。肿瘤组织中E-cadherin与IL-6表达呈负相关，IL-6与vimentin mRNA表达呈正相关，STAT 3磷酸化与IL-6表达呈正相关。重要的是，二甲双胍在荷瘤裸鼠中抑制肿瘤生长和远处转移，并在体外和体内逆转IL-6诱导的EMT。此外，我们发现阻断STAT 3磷酸化可能是二甲双胍抑制IL-6诱导的EMT的潜在机制。结论IL-6通过STAT 3磷酸化表达增强是肺腺癌发生EMT的机制之一。我们发现二甲双胍可能通过阻断STAT 3磷酸化而抑制IL-6诱导的EMT。
Objective Epithelial-mesenchymal transition (EMT) plays an important role in cancer tumorigenesis. However, the underlying mechanisms of EMT in lung adenocarcinoma, and how this process might be inhibited, remain to be explored. This study investigated the role of IL-6 in lung adenocarcinoma cell EMT and explored the potential effects of metformin on this process. Methods Invasion assay and MTT assay was performed to determine cell invasion and cell proliferation. Western blotting, immunofluorescence, real-time PCR, ELISA, and immunohistochemistry were performed to detect the expression of IL-6, E-cadherin, Vimentin, and p-STAT3. Results We discovered that IL-6, via STAT3 phosphorylation, could promote lung adenocarcinoma cell invasion via EMT in vitro. This was supported by the inverse correlation between E-cadherin and IL-6 expression, positive correlation between IL-6 and vimentin mRNA expression and between STAT3 phosphorylation and IL-6 expression in tumor tissues. Importantly, metformin inhibited tumor growth and distant metastases in tumor-bearing nude mice and reversed IL-6-induced EMT both in vitro and in vivo. Furthermore, we found that blockade of STAT3 phosphorylation might be the underlying mechanism of metformin inhibition of IL-6-induced EMT. Conclusions Collectively, our present results show that enhanced IL-6 expression, via STAT3 phosphorylation, is a mechanism of EMT in lung adenocarcinoma. We found that metformin could inhibit IL-6-induced EMT possibly by blocking STAT3 phosphorylation.
登录
查看更多内容
影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
影响因子：
50.3
作者：
Bromberg J;Wang TC
通讯作者：
Wang TC
DOI：
10.1152/ajpendo.00202.2013
发表时间：
2014-01-01
影响因子：
5.1
作者：
Li, Hongliang;Lee, Jiyeon;Xie, Zhonglin
通讯作者：
Xie, Zhonglin
影响因子：
11.1
作者：
Miguel Lopez-Novoa, Jose;Angela Nieto, M.
通讯作者：
Angela Nieto, M.
影响因子：
3.4
作者：
Dohadwala, Mariam;Wang, Guanyu;John, Maie A. St.
通讯作者：
John, Maie A. St.