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Downregulation of SPARC expression decreases gastric cancer cellular invasion and survival

DOI: 10.1186/1756-9966-29-59

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Abstract:

SPARC expression was evaluated in a panel of human gastric cancer cell lines. MGC803 and HGC 27 gastric cancer cell lines expressing high level of SPARC were transiently transfected with SPARC-specific small interfering RNAs and subsequently evaluated for effects on invasion and proliferation.Small interfering RNA-mediated knockdown of SPARC in MGC803 and HGC 27 gastric cancer cells dramatically decreased their invasion. Knockdown of SPARC was also observed to significantly increase the apoptosis of MGC803 and HGC 27 gastric cancer cells compared with control transfected group.Our data showed that downregulating of SPARC inhibits invasion and growth of human gastric cancer cells. Thus, targeting of SPARC could be an effective therapeutic approach against gastric cancer.Gastric cancer is the second leading cause of cancer-related deaths worldwide and is one of the most aggressive tumors and is frequently associated with lymph node metastasis, peritoneal dissemination, and hematogenous metastasis[1]. On the whole, 65-70% of new cases and deaths from gastric cancer occur in less-developed countries[2]. In 2005, the incidence rates of gastric cancer (0.3 million deaths and 0.4 million new cases) ranked third among the most common cancers in China[3]. Current therapies for advanced stage or metastatic gastric cancer have little effect, surgical removal with resection of adjacent lymph nodes offers the only chance for cure, which is less than 33% of patients with gastric cancer. The 5-year survival rate is only 30-40%, with a poorer prognosis for advanced tumours. Understanding the molecular mechanisms underlying the progression of gastric cancer may provide insights into new therapeutic targets.Secreted protein acidic and rich in cysteine (SPARC; also known as osteonectin or BM-40) belongs to the matricellular family of secreted proteins[4]. SPARC is a nonstructural component of extracellular matrices that modulates cell-matrix interactions, particularly during tissue de

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