title: Silencing of EphA2 inhibits invasion of human gastric cancer SGC-7901  cells in vitro and in vivo.
abstract: Receptor tyrosine kinases (RTKs), the common products of transforming oncogenes, have been widely used as indicators in the genesis and progression of human tumors. Until now, the erythropoietin-producing human hepatocellular (Eph) receptors have been recognized as the largest family of RTKs. EphA2, one member of Eph receptors, locates on human chromosome 1p36.1 which is a hot region for cancer research. It has been reported that high EphA2 expression levels were correlated with the tumor metastasis and poor prognosis. Increased expression of EphA2 can promote tumor growth and enhance the metastatic potential. To further define the function of EphA2 in malignant invasion, we employed the small interference RNA (siRNA) technique to knockdown gene expression of EphA2 in the gastric cancer SGC-7901 cell. Our results showed that the expression of double stranded RNA led to the efficient and specific inhibition of endogenous EphA2 expression in SGC-7901 cells. Silencing of EphA2 expression inhibited cell proliferation, caused cell cycle arrest, and decreased cell invasion in vitro. In addition, intratumoral injection EphA2 siRNA plasmid suppressed the growth of SGC-7901 cells xenografts in nude mice. Furthermore, knockdown of EphA2 expression reduced the expression of matrix metalloproteinase-9 (MMP-9) in vitro and in vivo. In conclusion, our findings demonstrate that silencing of EphA2 inhibits gastric cancer SGC-7901 cell proliferation, invasion and MMP-9 expression, which indicate that the specific inhibition of EphA2 may be a potential approach for gastric cancer therapy.
authors: Department of General Surgery, Central South University, Changsha, People's Republic of China.
authors: W
authors: W
authors: Yuan
authors: Z
authors: Z
authors: Chen
authors: Z
authors: Z
authors: Chen
authors: S
authors: S
authors: Wu
authors: J
authors: J
authors: Guo
authors: J
authors: J
authors: Ge
authors: P
authors: P
authors: Yang
authors: J
authors: J
authors: Huang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects / Q000473:pathology / Q000637:transplantation; D015536:Down-Regulation; D004790:Enzyme Induction / Q000187:drug effects; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D008081:Liposomes; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology* / Q000627:therapeutic use; D011897:Random Allocation; D036104:Receptor, EphA2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D023041:Xenograft Model Antitumor Assays
chemical_list: D008081:Liposomes; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D036104:Receptor, EphA2; D020780:Matrix Metalloproteinase 9