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

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.

• Authors: Ryohei Takahashi, Takashi Sato, Dennis M Klinman, Takeshi Shimosato, Takeshi Kaneko, Yoshiaki Ishigatsubo
• Journal: International journal of oncology (Int J Oncol) Vol. 42 Issue 2 Pg. 429-36 (Feb 2013) ISSN: 1791-2423 [Electronic] Greece
• PMID: 23291718 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Oligodeoxyribonucleotides
• Deoxycytidine
• Proto-Oncogene Proteins c-akt
• Paclitaxel
• Gemcitabine

Topics

• Antineoplastic Agents (administration & dosage)
• Apoptosis
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, pathology)
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Drug Synergism
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Lung Neoplasms (drug therapy, genetics, pathology)
• Oligodeoxyribonucleotides (administration & dosage, genetics)
• Paclitaxel (administration & dosage)
• Proto-Oncogene Proteins c-akt (genetics)
• Repetitive Sequences, Nucleic Acid
• Gemcitabine