Inhibitory effects of adenovirus mediated COX-2, Akt1 and PIK3R1 shRNA on the growth of malignant tumor cells in vitro and in vivo

  • Authors:
    • Yanchao Fu
    • Qingyu Zhang
    • Chunsheng Kang
    • Kairu Zhang
    • Jing Zhang
    • Peiyu Pu
    • Guangxiu Wang
    • Tao Wang
  • View Affiliations

  • Published online on: September 1, 2009     https://doi.org/10.3892/ijo_00000369
  • Pages: 583-591
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Abstract

Cyclooxygenase-2 (COX-2) and phosphatidylinositol 3-kinase (PI3K)/Akt play a critical role in the formation of many malignant tumors, and have been shown to be important therapeutic targets. In the present study, small hairpin RNA (shRNA) expression constructs that target sequences of human COX-2, Akt1 and PIK3R1 were used to examine the proliferation and invasion inhibition effects on SGC7901 gastric adenocarcinoma cells and U251 glioma cells. Cell growth was inhibited by over 70%, as indicated by a MTT assay, and was accompanied by G1/G0 phase arrest in the shRNA treated group, indicating poor cell growth activities. The number of cells invading through the matrigel in the shRNA treated group were significantly decreased (26.4±4.6) compared with that of the control group (105±4.0) and the nonsense sequence group (102.5±6.4). In addition, the tumor volumes in the SGC7901 subcutaneous nude mouse model treated with shRNA was significantly smaller than those of the control group and nonsense sequence group. When COX-2, Akt1 and PIK3R1 were dramatically downregulated, proliferating cell nuclear antigen (PCNA), CyclinD1 and matrix metalloproteinases (MMP-2, MMP-9) were downregulated, while tissue-inhibitor of metalloproteinase-2 (TIMP-2) and P53 were upregulated. Our results demonstrated that shRNA targeting COX-2, Akt1 and PIK3R1 downregulates their expression significantly in a sequence-specific manner, exerting proliferation and invasion inhibition effects on SGC7901 and U251 cells. In conclusion, our data suggest a novel mechanism for the regulation of malignant tumor cell growth and provide evidence for new combinatory gene therapy for malignant tumors.

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September 2009
Volume 35 Issue 3

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

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Spandidos Publications style
Fu Y, Zhang Q, Kang C, Zhang K, Zhang J, Pu P, Wang G and Wang T: Inhibitory effects of adenovirus mediated COX-2, Akt1 and PIK3R1 shRNA on the growth of malignant tumor cells in vitro and in vivo. Int J Oncol 35: 583-591, 2009
APA
Fu, Y., Zhang, Q., Kang, C., Zhang, K., Zhang, J., Pu, P. ... Wang, T. (2009). Inhibitory effects of adenovirus mediated COX-2, Akt1 and PIK3R1 shRNA on the growth of malignant tumor cells in vitro and in vivo. International Journal of Oncology, 35, 583-591. https://doi.org/10.3892/ijo_00000369
MLA
Fu, Y., Zhang, Q., Kang, C., Zhang, K., Zhang, J., Pu, P., Wang, G., Wang, T."Inhibitory effects of adenovirus mediated COX-2, Akt1 and PIK3R1 shRNA on the growth of malignant tumor cells in vitro and in vivo". International Journal of Oncology 35.3 (2009): 583-591.
Chicago
Fu, Y., Zhang, Q., Kang, C., Zhang, K., Zhang, J., Pu, P., Wang, G., Wang, T."Inhibitory effects of adenovirus mediated COX-2, Akt1 and PIK3R1 shRNA on the growth of malignant tumor cells in vitro and in vivo". International Journal of Oncology 35, no. 3 (2009): 583-591. https://doi.org/10.3892/ijo_00000369