Silencing of Rac3 Inhibits Proliferation and Induces Apoptosis of Human Lung Cancer Cells

Background: Rac3, a member of the Rac family of small guanosine triphosphatases (GTPases), regulatesa variety of cell functions, including the organization of the cytoskeleton, cell migration, and invasion.Overexpression of Rac3 has been reported in several human cancers. However, the role of Rac3 in lung cancer(LC) has not been determined in detail. The purpose of this study was to investigate the effect of silencing of Rac3expression in human LC cells and the consequences for cell survival. Materials and
Methods: Lentivirus smallhairpin RNA (shRNA) interference techniques were utilized to knock down the Rac3 gene. Gene and proteinexpression was quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting.LC cell apoptosis was examined by annexin V-APC /propidium iodide staining.
Results: Efficient silencing ofRac3 strongly inhibited A549 cell proliferation and colony formation ability, and significantly decreased tumorgrowth. Moreover, flow cytometry analysis showed that knockdown of Rac3 led to G2/M phase cell cycle arrestas well as an excess accumulation of cells in the G1 and S phase.
Conclusions: Thus, functional analysis usingshRNAs revealed a critical role for Rac3 in the tumor growth of LC cells. shRNA silencing of Rac3 could providean effective strategy to treat LC.