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Int J Mol Med. 2011 Nov;28(5):769-76. doi: 10.3892/ijmm.2011.775. Epub 2011 Aug 11.

Silencing of Rac1 modifies lung cancer cell migration, invasion and actin cytoskeleton rearrangements and enhances chemosensitivity to antitumor drugs.

Author information

1
Department of Respiratory Disease, The 117th Hospital of PLA, Hang Zhou, PR China. cqyong117@163.com

Abstract

Rac1, an intracellular signal transducer, regulates a variety of cell functions, including the organization of the cytoskeleton, cell migration, and invasion. Overexpression of Rac1 has been reported in several human cancers. However, the underlying mechanisms are not well understood. In the present study, we evaluated the possibility of Rac1 as an appropriate molecular target for cancer gene therapy. The expression of Rac1 in 150 primary non-small cell lung cancer tissues (NSCLC) and 30 normal paraneoplastic lung tissues was determined by immunohistochemical staining, and the correlation of Rac1 overexpression with clinicopathological factors was evaluated. Overexpression of Rac1 was detected in 94 of 150 lung cancer specimens, the incidence rate being higher than that in normal lung tissue specimens. In addition, overexpression of Rac1 was also associated with poor differentiation, high TNM stage, and lymph node metastasis in NSCLC patients. Moreover, RNAi-mediated suppression of Rac1 expression reduced lamellipodia formation, migration and invasion potential of a lung cancer cell carcinoma cell line, 801D. Down-regulation of Rac1 expression also reduced the expression of Pak1. NSC23766, an inhibitor of Rac1 activity, could also inhibit lung cancer cell migration, invasion and induce rearrangements of the actin cytoskeleton. Furthermore, the suppression of Rac1 expression also sensitized cells to antitumor drugs. These results indicate that the overexpression of Rac1 is tightly associated with an aggressive phenotype of lung cancer cells. Therefore, we proposed that Rac1 could be a potential molecular target of gene therapy by RNAi-targeting in lung cancer cells.

PMID:
21837360
DOI:
10.3892/ijmm.2011.775
[Indexed for MEDLINE]

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