Knockdown of RhoGDIα induces apoptosis and increases lung cancer cell chemosensitivity to paclitaxel

This study aimed to investigate the effects of RhoGDI alpha knockdown on apoptosis and the chemosensitivity of lung cancer cells to paclitaxel. The signaling proteins involved were also assessed. RhoGDI alpha expression was assessed by RT-PCR, Western blotting and immunohistochemistry. Apoptosis was determined by flow cytometric assessment, and cell viability was measured with the MTT assay. Phosphorylation levels of signaling proteins, ERK, JNK, Akt, Bad and I kappa B alpha were tested by Western blotting and immunohistochemistry. Positivity for RhoGDI alpha in lung cancer tissues was significantly higher than in paracancerous tissues. Downregulation of RhoGDI alpha was associated with significantly increased apoptosis and repressed cell viability. This effect could be due to the consequent upregulation of p-JNK, as well as decreased levels of p-ERK, p-Bad and p-I kappa B alpha. Knockdown of RhoGDI alpha strengthened the effect on apoptosis and inhibition of cell viability induced by paclitaxel treatment. This chemosensitization effect could be a result of the intensification of pro-apoptotic JNK activation, and repression of anti-apoptotic p-ERK, p-Bad and p-I kappa B alpha expression stimulated by paclitaxel. In summary, our study indicated that RhoGDI alpha could be a promising therapeutic target, and the combination of RhoGDI alpha siRNA and paclitaxel might be a valuable potential therapy for lung cancer treatment.