Open Access

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

  • Published online on: December 28, 2012     https://doi.org/10.3892/ijo.2012.1755
  • Pages: 429-436
  • Copyright: © Takahashi et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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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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February 2013
Volume 42 Issue 2

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

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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