Functional disruption of macrophage migration inhibitory factor (MIF) suppresses proliferation of human H460 lung cancer cells by caspase-dependent apoptosis.
Functional disruption of macrophage migration inhibitory factor (MIF) suppresses proliferation of human H460 lung cancer cells by caspase-dependent apoptosis.
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DOI：
10.1186/1475-2867-13-28
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发表时间：
2013-03-24
影响因子：
5.8
通讯作者：
Wang D
中科院分区：
文献类型：
--
作者：
Guo Y;Hou J;Luo Y;Wang D
巨噬细胞移动抑制因子（MIF）在调节正常细胞和癌细胞的细胞增殖和凋亡中起重要作用，并且可能在癌症的进展和转移中起重要作用。在人类非小细胞肺癌（NSCLC）中，负责细胞增殖和细胞死亡的MIF依赖性调节的潜在机制仍然认识不足。用最佳确定剂量的50 pmol/ml MIF siRNA处理人H460肺癌细胞系，随后分析细胞增殖、细胞周期和凋亡。此外，评估了已知的凋亡途径，包括Annexin-V的表达，半胱天冬酶-3和-4的增强产生以及Akt信号蛋白的表达，试图提供对MIF表达破坏后凋亡所涉及的信号通路的见解。与阴性对照相比，特异性siRNA序列显著降低H460细胞中MIF的表达2至5倍。此外，通过细胞表面Annexin-V表达评估，MIF miRNA不仅抑制细胞增殖，而且增加凋亡细胞的频率。细胞进入凋亡部分依赖于caspase-3和caspase-4的产生增加，而不影响caspase-8或Akt信号通路的表达。在非小细胞肺癌模型中，通过部分依赖于细胞进入凋亡并增加半胱氨酸蛋白酶-3和-4的产生的机制，抑制了MIF mRNA表达，从而抑制了H460的增殖。因此，MIF表达可能在NSCLC进展中起重要作用。靶向MIF可能在人类肺癌的管理中具有临床实用性。
Macrophage migration inhibitory factor (MIF) is important in regulating cell proliferation and apoptosis in both normal and cancerous cells, and may be important in cancer progression and metastasis. In human non-small cell lung cancer (NSCLC), the underlying mechanisms responsible for MIF-dependent regulation of cellular proliferation, and cell death remain poorly appreciated. The human H460 lung cancer cell-line was treated with an optimally determined dose of 50 pmol/ml MIF siRNA, following which cell proliferation, cell cycle and apoptosis were analyzed. Additionally, known pathways of apoptosis including expression of Annexin-V, enhanced production of caspases-3 and −4 and expression of the Akt signaling protein were assessed in an attempt to provide insights into the signaling pathways involved in apoptosis following disruption of MIF expression. Specific siRNA sequences markedly decreased MIF expression in H460 cells by 2 to 5-fold as compared with the negative control. Moreover, MIF miRNA dampened not only cellular proliferation, but increased the frequency of apoptotic cells as assessed by cell-surface Annexin-V expression. Entry of cells into apoptosis was partly dependent on enhanced production of caspases −3 and −4 while not affecting the expression of either caspase-8 or the Akt signaling pathway. In a model of NSCLC, knockdown of MIF mRNA expression dampened H460 proliferation by mechanisms partly dependent on entry of cells into apoptosis and enhanced production of caspase-3 and −4. MIF expression may thus be important in NSCLC progression. Targeting MIF may have clinical utility in the management of human lung cancer.
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DOI：
10.1084/jem.190.10.1375
发表时间：
1999-11-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hudson JD;Shoaibi MA;Maestro R;Carnero A;Hannon GJ;Beach DH
通讯作者：
Beach DH
影响因子：
7.8
作者：
Hitomi, Junichi;Katayama, Taiichi;Eguchi, Yutaka;Kudo, Takashi;Taniguchi, Manabu;Koyama, Yoshihisa;Manabe, Takayuki;Yamagishi, Satoru;Bando, Yoshio;Imaizumi, Kazunori;Tsujimoto, Yoshihide;Tohyama, Masaya
通讯作者：
Tohyama, Masaya
影响因子：
7.3
作者：
Lai, KN;Leung, JCK;Lan, HY
通讯作者：
Lan, HY
DOI：
10.1073/pnas.0701553104
发表时间：
2007-08-14
影响因子：
11.1
作者：
Binsky, Inbal;Haran, Michal;Shachar, Idit
通讯作者：
Shachar, Idit
影响因子：
32.4
作者：
Bucala, Richard;Donnelly, Seamas C.
通讯作者：
Donnelly, Seamas C.