Knockdown of RhoGDIα induces apoptosis and increases lung cancer cell chemosensitivity to paclitaxel.
This study aimed to investigate the effects of RhoGDIα knockdown on apoptosis and the chemosensitivity of lung cancer cells to paclitaxel. The signaling proteins involved were also assessed. RhoGDIα 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 IκBα were tested by Western blotting and immunohistochemistry. Positivity for RhoGDIα in lung cancer tissues was significantly higher than in paracancerous tissues. Downregulation of RhoGDIα 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-IκBα. Knockdown of RhoGDIα 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-IκBα expression stimulated by paclitaxel. In summary, our study indicated that RhoGDIα could be a promising therapeutic target, and the combination of RhoGDIα siRNA and paclitaxel might be a valuable potential therapy for lung cancer treatment.
Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
F
F
Rong
W
W
Li
K
K
Chen
D M
DM
Li
W M
WM
Duan
Y Z
YZ
Feng
F
F
Li
X W
XW
Zhou
S J
SJ
Fan
Y
Y
Liu
M
M
Tao
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D000072000:NF-KappaB Inhibitor alpha; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
D000972:Antineoplastic Agents, Phytogenic; D020730:Guanine Nucleotide Dissociation Inhibitors; D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; D000072000:NF-KappaB Inhibitor alpha; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D017239:Paclitaxel