Inhibition of Stat3 activation and tumor growth suppression of non-small cell lung cancer by G-quartet oligonucleotides

  • Authors:
    • Priya Weerasinghe
    • Gabriela E. Garcia
    • Qiqing Zhu
    • Ping Yuan
    • Lili Feng
    • Li Mao
    • Naijie Jing
  • View Affiliations

  • Published online on: Sunday, July 1, 2007
  • Pages: 129-136
  • DOI: 10.3892/ijo.31.1.129

Abstract

Lung cancer is the leading cause of cancer mortality in the United States. Despite advances made over the past decades, the overall survival of patients with lung cancer remains dismal. Here we report novel G-quartet oligodeoxynucleotides (GQ-ODN) that were designed to selectively target signal transducer and activator of transcription 3 (Stat3), in the treatment of human non-small cell lung cancer (NSCLC). The objective of this study was to evaluate the effects of two novel GQ-ODN STAT3 inhibitors, T40214 and T40231, on NSCLC bearing nude mice. NSCLC bearing nude mice were assigned to 5 groups, which were treated by vehicle, control ODN, T40214, T40231, and Paclitaxel, respectively. Tumors were measured, isolated and analyzed using Western blotting, immuno-histochemistry, RPA and TUNEL. Results show that GQ-ODN T40214 and T40231 significantly suppress the growth of NSCLC tumors in nude mice by selectively inhibiting the activation of Stat3 and its downstream proteins Bcl-2, Bcl-xL, Mcl-1, survivin, VEGF, Cyclin D1 and c-myc; thereby, promoting apoptosis and reducing angiogenesis and cell proliferation. These findings validate Stat3 as an important molecular target for NSCLC therapy and demonstrate the efficacy of GQ-ODN in inhibiting Stat3 phosphorylation.
Journal Cover

July 2007
Volume 31 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

2013 Impact Factor: 2.773
Ranked #30/202 Oncology
(total number of cites)

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APA
Weerasinghe, P., Garcia, G., Zhu, Q., Yuan, P., Feng, L., Mao, L., & Jing, N. (2007). Inhibition of Stat3 activation and tumor growth suppression of non-small cell lung cancer by G-quartet oligonucleotides. International Journal of Oncology, 31(1), 129-136.
MLA
Weerasinghe, Garcia, Zhu, Yuan, Feng, Mao, and Naijie Jing. "Inhibition of Stat3 activation and tumor growth suppression of non-small cell lung cancer by G-quartet oligonucleotides." International Journal of Oncology International Journal of Oncology 31.1 (2007): 129-136.
Chicago
Weerasinghe, Garcia, Zhu, Yuan, Feng, Mao, and Naijie Jing. "Inhibition of Stat3 activation and tumor growth suppression of non-small cell lung cancer by G-quartet oligonucleotides." International Journal of Oncology International Journal of Oncology 31 no. 1 (2007): 129-136.