Irisin inhibits pancreatic cancer cell growth via the AMPK-mTOR pathway.
Irisin inhibits pancreatic cancer cell growth via the AMPK-mTOR pathway.
复制标题
DOI：
10.1038/s41598-018-33229-w
复制
发表时间：
2018-10-15
影响因子：
4.6
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Liu J;Song N;Huang Y;Chen Y
鸢尾素是最近发现的一种肌肉因子，它在运动后从骨骼肌中释放出来，可以调节体重，并影响肥胖和糖尿病等各种代谢疾病。本研究比较了人重组非糖基化p -鸢尾素（在大肠杆菌原核细胞系统中表达）和糖基化e -鸢尾素（在毕赤酵母真核细胞系统中表达）对胰腺癌（PC）细胞株、MIA PaCa-2和Panc03.27的作用。MTT[3-（4,5 -二甲基噻唑-2-基）- 2,5 -二苯基溴化四唑]和细胞集落形成实验显示，鸢尾素显著抑制MIA PaCa-2和Panc03.27的生长，且呈剂量依赖性。鸢尾素还能诱导两种细胞系的G1阻滞。划痕伤口愈合和transwell实验显示鸢尾素也能抑制PC细胞的迁移。鸢尾素可逆转上皮-间质转化（EMT）活性，增加E-cadherin表达，降低vimentin表达。鸢尾素激活单磷酸腺苷活化蛋白激酶（AMPK）通路，抑制哺乳动物雷帕霉素（mTOR）信号通路。此外，我们的研究结果表明鸢尾素受体存在于人MIA PaCa-2和Panc03.27细胞表面。我们的研究结果清楚地表明，鸢尾素通过激活AMPK抑制PC细胞的生长，从而下调mTOR通路，抑制PC细胞的EMT。
Irisin, a recently identified myokine that is released from skeletal muscle following exercise, regulates body weight and influences various metabolic diseases such as obesity and diabetes. In this study, human recombinant nonglycosylated P-irisin (expressed in Escherichia coli prokaryote cell system) or glycosylated E-irisin (expressed in Pichia pastoris eukaryote cell system) were compared to examine the role of recombinant irisin against pancreatic cancer (PC) cells lines, MIA PaCa-2 and Panc03.27. MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-di phenyltetrazolium bromide] and cell colony formation assays revealed that irisin significantly inhibited the growth of MIA PaCa-2 and Panc03.27 in a dose-dependent manner. Irisin also induced G1 arrest in both cell lines. Scratch wound healing and transwell assays revealed that irisin also inhibited the migration of PC cells. Irisin reversed the activity of epithelial–mesenchymal transition (EMT) while increasing E-cadherin expression and reducing vimentin expression. Irisin activated the adenosine monophosphate-activated protein kinase (AMPK) pathway and suppressed the mammalian target of rapamycin (mTOR) signaling. Besides, our results suggest that irisin receptors exist on the surface of human MIA PaCa-2 and Panc03.27 cells. Our results clearly demonstrate that irisin suppressed PC cell growth via the activation of AMPK, thereby downregulating the mTOR pathway and inhibiting EMT of PC cells.
登录
查看更多内容
影响因子：
3.7
作者：
Gao S;Li S;Ma Z;Liang S;Shan T;Zhang M;Zhu X;Zhang P;Liu G;Zhou F;Yuan X;Jia R;Potempa J;Scott DA;Lamont RJ;Wang H;Feng X
通讯作者：
Feng X
影响因子：
5.2
作者：
Casari I;Falasca M
通讯作者：
Falasca M
影响因子：
--
作者：
Lee, Hye Jeong;Lee, Jung Ok;Kim, Hyeon Soo
通讯作者：
Kim, Hyeon Soo
影响因子：
6.6
作者：
Cazarin, Juliana M.;Coelho, Raquel G.;Carvalho, Denise P.
通讯作者：
Carvalho, Denise P.
影响因子：
4.7
作者：
Karamitopoulou E
通讯作者：
Karamitopoulou E