Knockdown of NF-κB p65 subunit expression suppresses growth of nude mouse lung tumour cell xenografts by inhibition of Bcl-2 apoptotic pathway.

Abstract

Nuclear factor-kappaB (NF-κB) is an important transcriptional factor and regulates a variety of pathophysiologic process involved in cell survival and death. This study aimed to assess the effects of NF-κB p65 subunit knockdown in suppression of nude mouse lung tumour cell xenografts and understands the underlying molecular events. A nude mouse Lewis lung carcinoma cell xenograft model was established, and the mice were intraperitoneally injected with NF-κB p65 small interfering RNA (siRNA) and sacrificed after 2weeks of tumour cell injection. Tumour xenografts were harvested for terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, Western blot and quantitative reverse transcription-polymerase chain reaction analyses. Results found that compared to the phosphate-buffered saline (PBS)-treated or the negative control (NC) siRNA-treated mice tumour xenograft weight and volume were significantly decreased in the NF-κB p65 siRNA-treated mice. The TUNEL positive (apoptosis) cells in xenograft sections were 45 ± 5 in PBS and 38 ± 3 in NC siRNA but increased to 271 ± 11 in p65 siRNA-treated mice. Compared to the PBS or the NC mice, levels of Bcl-2 mRNA and protein in tumour xenografts were significantly downregulated in p65 siRNA-treated mice. Knockdown of NF-κB p65 subunit expression can significantly inhibit the growth of nude mouse Lewis tumour cell xenografts by inducing tumour cell apoptosis and downregulating pro-apoptotic protein Bcl-2 expression. Targeting NF-κB p65 subunit expression as a potential therapeutic strategy needs further evaluation in treating human lung cancer.

• Authors: Yun Qu, Bo Qu, Xiaofang Wang, Rong Wu, Xiaoye Zhang
• Journal: Cell biochemistry and function (Cell Biochem Funct) Vol. 33 Issue 5 Pg. 320-5 (Jul 2015) ISSN: 1099-0844 [Electronic] England
• PMID: 26178579 (Publication Type: Journal Article)
• Copyright: Copyright © 2015 John Wiley & Sons, Ltd.

Chemical References

• Bclaf1 protein, mouse
• RNA, Small Interfering
• Repressor Proteins
• Transcription Factor RelA

Topics

• Animals
• Apoptosis (drug effects)
• Carcinoma, Lewis Lung (genetics, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Gene Expression (drug effects)
• Gene Knockdown Techniques
• Heterografts
• Lung Neoplasms (genetics, pathology)
• Mice, Inbred C57BL
• Mice, Nude
• RNA, Small Interfering (pharmacology)
• Repressor Proteins (metabolism)
• Transcription Factor RelA (genetics, metabolism)