Therefore, the regulation of Bcl-2 and Bax expression may be a key mechanism underlying SPARC induction of apoptosis in gastric cancer cells. So our data
indicated that downregulation of SPARC inhibited cell proliferation of gastric cancer cells by apoptosis initiation, which conscience with melanoma and glioma, but contrary to ovarian and pancreatic cancer. The induction of apoptosis was partly regulated to mitochondrial pathway such Selleck MCC950 as activation caspase pathway as well as cleavage of PARP. Future study needs to focus on the exact mechanism. In conclusion, our current data suggested that SPARC played important roles in apoptosis and metastasis of gastric cancer. At present, there are no effective approaches for curing late stage gastric cancer. As elevated SPARC expression is associated with decreased gastric cancer patient
survival, we believe that our results, demonstrating decreased invasion and increased cell death with siRNA directed against SPARC, suggest that decreasing SPARC expression may have therapeutic benefit for gastric cancer patients. Acknowledgements This work was supported by the National Scientific Technologic Supporting Project Fund. We thank Professor Yang Ke and Xiaojuan Du of Peking University Health Science Centre, Beijing, China, for technical support. References 1. International Agency for Research on Cancer (2004) Globocan 2002: Cancer Incidence, Mortality and Prevalence Worldwide, version 2.0. Tyrosine-protein kinase BLK In IARC CancerBase no. 5. Edited by: Ferlay J, Bray F, Pisani P, Parkin DM. Lyon, France: IARC Press; 2. Parkin DM, Bray F, Ferlay J, MLN2238 Pisani P: Global cancer statistics, 2002. CA Cancer J Clin 2005,55(2):74–108.PubMedCrossRef 3. Wu Chun-xiao ZYBP: Pattern of changing incidence of gastric cancer and its time trend in Shanghai. 2008, 13:24–29. 4. Yan Q, Sage EH: SPARC, a matricellular glycoprotein with important biological functions. J Histochem Cytochem 1999,47(12):1495–1505.PubMed 5. Bradshaw AD, Sage EH: SPARC, a matricellular protein
that GS-4997 in vitro functions in cellular differentiation and tissue response to injury. J Clin Invest 2001,107(9):1049–1054.PubMedCrossRef 6. Podhajcer OL, Benedetti LG, Girotti MR, Prada F, Salvatierra E, Llera AS: The role of the matricellular protein SPARC in the dynamic interaction between the tumor and the host. Cancer Metastasis Rev 2008,27(4):691–705.PubMedCrossRef 7. Porter PL, Sage EH, Lane TF, Funk SE, Gown AM: Distribution of SPARC in normal and neoplastic human tissue. J Histochem Cytochem 1995,43(8):791–800.PubMed 8. Thomas R, True LD, Bassuk JA, Lange PH, Vessella RL: Differential expression of osteonectin/SPARC during human prostate cancer progression. Clin Cancer Res 2000,6(3):1140–1149.PubMed 9. Ledda F, Bravo AI, Adris S, Bover L, Mordoh J, Podhajcer OL: The expression of the secreted protein acidic and rich in cysteine (SPARC) is associated with the neoplastic progression of human melanoma. J Invest Dermatol 1997,108(2):210–214.