MicroRNAs reduce tumor growth and contribute to enhance cytotoxicity induced by gefitinib in non-small cell lung cancer

Chemico-biological Interactions
Miao ZhongLing Chen

Abstract

MicroRNAs (miRNAs) have emerged as key post-transcriptional regulators of gene expression, involved in diverse physiological and pathological processes. An oncogenic or tumor-suppressive miRNA may have potential as a therapeutic target to control cancers. Gefitinib is a tyrosine kinase inhibitor that targets epidermal growth factor receptor (EGFR). H460 and A549 cells with EGFR receptor-independent over-activation of protein kinase B (Akt) or extracellular signal-regulated kinases (ERK) are significantly resistant to gefitinib. The first aim of this study was to confirm a role for three miRNAs (let-7a, hsa-miR-126, and hsa-miR-145) in the inhibition of proliferation in non-small cell lung cancer (NSCLC) cells. A second aim was to evaluate three miRNAs for their abilities to overcome cellular resistance and enhance the gefitinib cytotoxicity. The expression of miRNAs was estimated by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cell proliferation was examined by sulforhodamine B assay and tumor xenografts were measured in SCID/beige mice. The activation of Akt and ERK was observed by Western blotting. Forced expression of individual miRNA suppressed the growth of two cell lines and xenografts...Continue Reading

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