Functional disruption of macrophage migration inhibitory factor MIF suppresses proliferation of human H460 lung cancer cells by caspase-dependent apoptosisReport as inadecuate




Functional disruption of macrophage migration inhibitory factor MIF suppresses proliferation of human H460 lung cancer cells by caspase-dependent apoptosis - Download this document for free, or read online. Document in PDF available to download.

Cancer Cell International

, 13:28

First Online: 24 March 2013Received: 24 September 2012Accepted: 28 February 2013

Abstract

BackgroundMacrophage 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.

MethodsThe 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.

ResultsSpecific 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.

ConclusionsIn 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.

KeywordsMacrophage migration inhibitory factor MIF Non-small cell lung cancer Proliferation Apoptosis Caspase-3 Caspase-4 AbbreviationsMIFMacrophage migration inhibitory factor

siRNASmall interfering RNA

ER-stressEndoplasmic Reticulum Stress

PIPropidium iodide

PI3KPhosphoinositide 3-kinase

AKt-PKBProtein Kinase

Electronic supplementary materialThe online version of this article doi:10.1186-1475-2867-13-28 contains supplementary material, which is available to authorized users.

An erratum to this article is available at http:-dx.doi.org-10.1186-1475-2867-13-84.

Download fulltext PDF



Author: Yubiao Guo - Junna Hou - Yifeng Luo - Dujuan Wang

Source: https://link.springer.com/







Related documents