ABSTRACT
OBJECTIVE: To evaluate the anti-tumor effect of the combination of suberoylanilide hydroxamic acid(SAHA) with statins(lovastatin or simvastatin) on non-small cell lung carcinoma(NSCLC) cells. METHODS: Human NSCLC A549 cells were treated with SAHA in combination of lovastatin or simvastatin. The cell growth was analyzed by SRB method, and the apoptosis of A549 cells was assessed by flow cytometer. The expression of cleaved poly-ADP-ribose polymerase(cleaved-PARP) and p21 protein was analyzed by Western-blotting when A549 cells were challenged with 2.5µmol/L SAHA and 5µmol/L lovastatin. RESULTS: Lovastatin and simvastatin synergized SAHA in the inhibition of A549 cells. SAHA induced apoptosis was also enhanced by lovastatin. Treatment with 2.5µmol/L SAHA significantly up-regulated the expression of p21 protein in 48 h, while the protein expression was reduced in combined treatment with 5µmol/L lovastatin. CONCLUSION: Statins can synergize the anti-tumor effect of SAHA in human NSCLC cells through a p21-dependent way.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis , Carcinoma, Non-Small-Cell Lung/pathology , Hydroxamic Acids/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Cell Line, Tumor/drug effects , Cell Proliferation , Cyclin-Dependent Kinase Inhibitor p21/metabolism , Humans , Poly(ADP-ribose) Polymerases/metabolism , VorinostatABSTRACT
In the present study, we characterized the transcriptional regulatory region (KF038144) controlling the expression of a constitutive FAD2 in Brassica napus. There are multiple FAD2 gene copies in B. napus genome. The FAD2 gene characterized and analyzed in the study is located on chromosome A5 and was designated as BnFAD2A5-1. BnFAD2A5-1 harbors an intron (1,192 bp) within its 5'-untranslated region (5'-UTR). This intron demonstrated promoter activity. Deletion analysis of the BnFAD2A5-1 promoter and intron through the ß-glucuronidase (GUS) reporter system revealed that the -220 to -1 bp is the minimum promoter region, while -220 to -110 bp and +34 to +285 bp are two important regions conferring high-levels of transcription. BnFAD2 transcripts were induced by light, low temperature, and abscisic acid (ABA). These observations demonstrated that not only the promoter but also the intron are involved in controlling the expression of the BnFAD2A5-1 gene. The intron-mediated regulation is an essential aspect of the gene expression regulation.
