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Suppressive oligodeoxynucleotides synergistically enhance antiproliferative effects of anticancer drugs in A549 human lung cancer cells

  • Authors:
    • Ryohei Takahashi
    • Takashi Sato
    • Dennis M. Klinman
    • Takeshi Shimosato
    • Takeshi Kaneko
    • Yoshiaki Ishigatsubo
  • View Affiliations / Copyright

    Affiliations: Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, Yokohama 236‑0004, Japan, Center for Cancer Research, Cancer and Inflammation Program, National Cancer Institute at Frederick, Frederick, MD 21702, USA, Graduate School of Agriculture, Shinshu University, Nagano 399-4598, Japan
    Copyright: © Takahashi et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 429-436
    |
    Published online on: December 28, 2012
       https://doi.org/10.3892/ijo.2012.1755
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Abstract

Immunosuppressive oligodeoxynucleotides (Sup ODNs) containing repetitive TTAGGG motifs reduce inflammation and, thus, may have an impact on inflammation‑related tumor growth. In this study, we found a significant antiproliferative effect of Sup ODNs on the A549 non‑small cell lung cancer (NSCLC) cell line compared to those treated with control ODNs (p<0.05). Sup-ODN-mediated G1 phase cell cycle arrest was achieved via inhibition of Akt and extracellular signal-regulated kinase 1/2 phosphorylation and the p15INK4b and p27KIP1/retinoblastoma protein pathway. In addition, Sup ODNs induced apoptosis and enhanced apoptosis when combined with vinorelbine. In a setting similar to clinical use of multidrug chemotherapy for advanced NSCLC, these effects were investigated by using Sup ODNs in combination with conventional anticancer drugs. Sup ODNs had a significant synergistic effect with 5-fluorouracil, vinorelbine, gemcitabine, paclitaxel and irinotecan, with a mean combination index of 0.43-0.78 (<1.0 indicates synergism) in the A549 NSCLC cell line. In conclusion, our results showed that Sup ODNs have an anticancer effect and increase the sensitivity of NSCLC cells to conventional anticancer drugs by modifying Akt and the extracellular signal-regulated kinase 1/2 pathway. Thus, Sup ODNs may serve as a novel therapeutic strategy for NSCLC patients.
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Copy and paste a formatted citation
Spandidos Publications style
Takahashi R, Sato T, Klinman DM, Shimosato T, Kaneko T and Ishigatsubo Y: Suppressive oligodeoxynucleotides synergistically enhance antiproliferative effects of anticancer drugs in A549 human lung cancer cells. Int J Oncol 42: 429-436, 2013.
APA
Takahashi, R., Sato, T., Klinman, D.M., Shimosato, T., Kaneko, T., & Ishigatsubo, Y. (2013). Suppressive oligodeoxynucleotides synergistically enhance antiproliferative effects of anticancer drugs in A549 human lung cancer cells. International Journal of Oncology, 42, 429-436. https://doi.org/10.3892/ijo.2012.1755
MLA
Takahashi, R., Sato, T., Klinman, D. M., Shimosato, T., Kaneko, T., Ishigatsubo, Y."Suppressive oligodeoxynucleotides synergistically enhance antiproliferative effects of anticancer drugs in A549 human lung cancer cells". International Journal of Oncology 42.2 (2013): 429-436.
Chicago
Takahashi, R., Sato, T., Klinman, D. M., Shimosato, T., Kaneko, T., Ishigatsubo, Y."Suppressive oligodeoxynucleotides synergistically enhance antiproliferative effects of anticancer drugs in A549 human lung cancer cells". International Journal of Oncology 42, no. 2 (2013): 429-436. https://doi.org/10.3892/ijo.2012.1755
Copy and paste a formatted citation
x
Spandidos Publications style
Takahashi R, Sato T, Klinman DM, Shimosato T, Kaneko T and Ishigatsubo Y: Suppressive oligodeoxynucleotides synergistically enhance antiproliferative effects of anticancer drugs in A549 human lung cancer cells. Int J Oncol 42: 429-436, 2013.
APA
Takahashi, R., Sato, T., Klinman, D.M., Shimosato, T., Kaneko, T., & Ishigatsubo, Y. (2013). Suppressive oligodeoxynucleotides synergistically enhance antiproliferative effects of anticancer drugs in A549 human lung cancer cells. International Journal of Oncology, 42, 429-436. https://doi.org/10.3892/ijo.2012.1755
MLA
Takahashi, R., Sato, T., Klinman, D. M., Shimosato, T., Kaneko, T., Ishigatsubo, Y."Suppressive oligodeoxynucleotides synergistically enhance antiproliferative effects of anticancer drugs in A549 human lung cancer cells". International Journal of Oncology 42.2 (2013): 429-436.
Chicago
Takahashi, R., Sato, T., Klinman, D. M., Shimosato, T., Kaneko, T., Ishigatsubo, Y."Suppressive oligodeoxynucleotides synergistically enhance antiproliferative effects of anticancer drugs in A549 human lung cancer cells". International Journal of Oncology 42, no. 2 (2013): 429-436. https://doi.org/10.3892/ijo.2012.1755
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