Abstract
Gliomas are the most common type of primary brain tumors. Despite the improvement in current treatments for gliomas, including surgical resection, radiation, and chemotherapy, there has been very little progress in curing this kind of disease. Stat3 is a member of signal transducer and activator of transcription family. It plays an important role in regulating cell survival, invasion, and apoptosis. This study investigated the influence of low-level expression of Stat3 on invasion and apoptosis in U251 cells. Our data showed that Stat3 is constitutively expressed in human gliomas cell line U251. The invasion activity in U251 cells was weakened and the apoptosis in U251 cells was induced after down-regulation of Stat3. In addition, down-regulation of Stat3 can suppress the expression of MMP-2, Bcl-xL and survivin but not 67LR. These results further indicate that Stat3 plays a key role in the invasion and apoptosis of human glioma cell line U251.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ambrosini G, Adida C, Altieri DC (1997) A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 3:917–921
Bowman T, Garcia R, Turkson J, Jove R (2000) STATs in oncogenesis. Oncogene 19:2474–2488
Bromberg J (2002) Stat proteins and oncogenesis. J Clin Invest 109:1139–1142
Bromberg JF, Wrzeszczynska MH, Devgan G, Zhao Y, Pestell RG, Albanese C et al (1999) Stat3 as an oncogene. Cell 98:295–303
Catlett-Falcone R, Landowski TH, Oshiro MM, Turkson J, Levitzki A, Savino R et al (1999) Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells. Immunity 10:105–115
Chen F, Guo Q, Yang Y, Song H, Wen T (2005) Inhibition of AF116909 gene expression enhances the differentiation of neural stem cells. Neurol Res 27:557–561
Chen FX, Qian YR, Duan YH, Ren WW, Yang Y, Zhang CC et al (2009) Down-regulation of 67LR reduces the migratory activity of human glioma cells in vitro. Brain Res Bull 79:402–408
Darnell JE Jr (1997) STATs and gene regulation. Science 277:1630–1635
Gao L, Zhang L, Hu J, Li F, Shao Y, Zhao D et al (2005) Down-regulation of signal transducer and activator of transcription 3 expression using vector-based small interfering RNAs suppresses growth of human prostate tumor in vivo. Clin Cancer Res 11:6333–6341
Gu J, Li G, Sun T, Su Y, Zhang X, Shen J et al (2008) Blockage of the STAT3 signaling pathway with a decoy oligonucleotide suppresses growth of human malignant glioma cells. J Neuro-oncol 89:9–17
Huang C, Cao J, Huang KJ, Zhang F, Jiang T, Zhu L et al (2006) Inhibition of STAT3 activity with AG490 decreases the invasion of human pancreatic cancer cells in vitro. Cancer Sci 97:1417–1423
Jung S, Rutka JT, Hinek A (1998) Tropoelastin and elastin degradation products promote proliferation of human astrocytoma cell lines. J Neuropathol Exp Neurol 57:439–448
Jung S, Hinek A, Tsugu A, Hubbard SL, Ackerley C, Becker LE et al (1999) Astrocytoma cell interaction with elastin substrates: implications for astrocytoma invasive potential. Glia 25:179–189
Konnikova L, Kotecki M, Kruger MM, Cochran BH (2003) Knockdown of STAT3 expression by RNAi induces apoptosis in astrocytoma cells. BMC Cancer 3:23–32
Levy DE, Lee CK (2002) What does Stat3 do? J Clin Invest 109:1143–1148
Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A et al (2007) The 2007 WHO classification of tumors of the central nervous system. Acta Neuropathol 114:97–109
Nam S, Buettner R, Turkson J, Kim D, Cheng JQ, Muehlbeyer S et al (2005) Indirubin derivatives inhibit Stat3 signaling and induce apoptosis in human cancer cells. Proc Natl Acad Sci USA 102:5998–6003
Ohgaki H, Kleihues P (2005) Epidemiology and etiology of gliomas. Acta Neuropathol 109:93–108
Ren W, Duan Y, Yang Y, Ji Y, Chen F (2008) Down-regulation of Stat3 induces apoptosis of human glioma cell: a potential method to treat brain cancer. Neurol Res 30:297–301
Sambrook J, Russell DW (2001) Molecular cloning: a laboratory manual, 3rd edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor
Schwartzbaum JA, Fisher JL, Aldape KD, Wrensch M (2006) Epidemiology and molecular pathology of glioma. Nat Clin Pract Neurol 2:494–503
Shinozawa I, Inokuchi K, Wakabayashi I, Dan K (2000) Disturbed expression of the anti-apoptosis gene, survivin, and EPR-1 in hematological malignancies. Leuk Res 24:965–970
Takeda K, Clausen BE, Kaisho T, Tsujimura T, Terada N, Förster I et al (1999) Enhanced Th1 activity and development of chronic enterocolitis in mice devoid of Stat3 in macrophages and neutrophils. Immunity 10:39–49
Wechsler-Reya R, Scott MP (2001) The developmental biology of brain tumors. Annu Rev Neurosci 24:385–428
Wen PY, Kesari S (2008) Malignant gliomas in adults. N Engl J Med 359:492–507
Wen Z, Zhong Z, Darnell JE Jr (1995) Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosphorylation. Cell 82:241–250
Williams JG (2000) STAT signalling in cell proliferation and in development. Curr Opin Genet Dev 10:503–507
Xie TX, Wei D, Liu M, Gao AC, Ali-Osman F, Sawaya R et al (2004) Stat3 activation regulates the expression of matrix metalloproteinase-2 and tumor invasion and metastasis. Oncogene 23:3550–3560
Xie TX, Huang FJ, Aldape KD, Kang SH, Liu M, Gershenwald JE et al (2006) Activation of Stat3 in human melanoma promotes brain metastasis. Cancer Res 66:3188–3196
Yang Y, Ren W, Chen F (2006) Knockdown of Stat3 in C17.2 neural stem cells facilitates the generation of neurons: a possibility of transplantation with a low level of oncogene. NeuroReport 17:235–238
Zushi S, Shinomura Y, Kiyohara T, Miyazaki Y, Kondo S, Sugimachi M et al (1998) STAT3 mediates the survival signal in oncogenic ras-transfected intestinal epithelial cells. Int J Cancer 78:326–330
Acknowledgment
This study was supported by a Chinese Basic Research Grant “973” (no. 2006CB500801).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Chen, F., Xu, Y., Luo, Y. et al. Down-Regulation of Stat3 Decreases Invasion Activity and Induces Apoptosis of Human Glioma Cells. J Mol Neurosci 40, 353–359 (2010). https://doi.org/10.1007/s12031-009-9323-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12031-009-9323-3