A small interfering RNA targeting osteopontin as gastric cancer therapeutics.
It has been shown that Osteopontin (OPN) protein is overexpressed in the majority of gastric cancers and associated with its pathogenesis. To better understanding of the role of OPN, RNA interference (RNAi) was used to inhibit OPN expression in the human gastric cancer cells in vitro and in vivo. BGC-823, gastric cancer cell line, was stably transfected with OPN small interfering RNA (siRNA) plasmids. OPN siRNA significantly reduced the expression of OPN in human gastric cancer cells in transient- and stable-transfection manner. In vitro down-regulation of OPN inhibited BGC-823 cell growth, anchorage-independent growth, migration and invasion. The results further showed that OPN small interfering RNA suppressed the growth, migration and invasion of gastric cancer cell through the reduction of MMP-2 and uPA expression, inhibition of NF-kappaB DNA binding activity, and down-regulation of Akt phosphorylation. In vivo animal studies showed that tumor growth was significantly inhibited in OPN siRNA group compared with WT. Intratumor gene therapy with polyethylenimine/OPNsi also resulted in tumor growth suppression and prolonged survival. Thus, this study demonstrated that down-regulation of OPN could suppress the growth, migration and invasion of gastric cancer cells, and OPN siRNA may offer a new potential gene therapy approach for human gastric cancer in future.
Gong
Mouchun
M
Department of General Surgery, Changhai Hospital, The Second Military Medical University, Shanghai 200433, PR China.
Lu
Zhengmao
Z
Fang
Guoen
G
Bi
Jianwei
J
Xue
Xuchao
X
D002455:Cell Division; D045744:Cell Line, Tumor; D002465:Cell Movement; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics; D015536:Down-Regulation; D024202:Electrophoretic Mobility Shift Assay; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D009361:Neoplasm Invasiveness; D053495:Osteopontin / Q000235:genetics*; D010957:Plasmids / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D014162:Transfection
D017931:DNA Primers; D004273:DNA, Neoplasm; D034741:RNA, Small Interfering; D053495:Osteopontin