Rsf-1 Influences the Sensitivity of Non-Small Cell Lung Cancer to Paclitaxel by Regulating NF-κB Pathway and Its Downstream Proteins.

Abstract

BACKGROUND/AIMS:

The therapeutic efficacy of paclitaxel is hampered by chemotherapeutic resistance in non-small cell lung cancer (NSCLC). Rsf-1 enhanced paclitaxel resistance via nuclear factor-κB (NF-κB) in ovarian cancer cells and nasopharyngeal carcinoma. This study assessed the function of Rsf-1 in the modulation of the sensitivity of NSCLC to paclitaxel via the NF-κB pathway.

METHODS:

The mRNA and protein levels of the related genes were quantified by RT-PCR and Western blotting. Rsf-1 silencing was achieved with CRISPR/Cas9 gene editing. Cell cycle, migration and proliferation were tested with flow cytometry, transwell test and CCK8 test. Cell apoptosis was analyzed with flow cytometry and quantification of C-capase3. The parameters of the tumors were measured in H460 cell xenograft mice.

RESULTS:

Rsf-1 was highly expressed in H460 and H1299 cells. Rsf-1 knockout caused cell arrest at the G1 phase, increased cell apoptosis, and decreased migration and cell proliferation. Rsf-1 knockout increased the inhibition of cell proliferation, the reduction in cell migration and the augment in cell apoptosis in paclitaxel treated H460 and H1299 cells. Rsf-1 knockout further enhanced the paclitaxel-mediated decrease in the volume and weight of the tumors in H460 cell xenograft mice. Helenalin and Rsf-1 knockout decreased the protein levels of p-P65, BcL2, CFLAR, and XIAP; hSNF2H knockout decreased the protein level of NF-κB p-P65 without altering Rsf-1 and p65 protein levels, while Rsf-1 and hSNF2H double knockout decreased the level of NF-κB p-P65, in H1299 and H460 cells.

CONCLUSION:

These results demonstrate that Rsf-1 influences the sensitivity of NSCLC to paclitaxel via regulation of the NF-κB pathway and its downstream genes.

• Authors: Xitao Chen, Xiaodi Sun, Jingqian Guan, Junda Gai, Jilin Xing, Lin Fu, Shuli Liu, Feifei Shen, Keyan Chen, Wenya Li, Libo Han, Qingchang Li
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 44 Issue 6 Pg. 2322-2336 ( 2017) ISSN: 1421-9778 [Electronic] Germany
• PMID: 29258089 (Publication Type: Journal Article)
• Copyright: © 2017 The Author(s). Published by S. Karger AG, Basel.

Chemical References

• Antineoplastic Agents, Phytogenic
• NF-kappa B
• Nuclear Proteins
• RSF1 protein, human
• Trans-Activators
• Paclitaxel

Topics

• Animals
• Antineoplastic Agents, Phytogenic (pharmacology, therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, pathology)
• Cell Line, Tumor
• Drug Resistance, Neoplasm
• Female
• Gene Knockout Techniques
• Humans
• Lung (drug effects, metabolism, pathology)
• Lung Neoplasms (drug therapy, genetics, pathology)
• Mice, Nude
• NF-kappa B (metabolism)
• Nuclear Proteins (genetics, metabolism)
• Paclitaxel (pharmacology, therapeutic use)
• Signal Transduction
• Trans-Activators (genetics, metabolism)