title: 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.affiliation: Department of Internal Medicine and Clinical Immunology, Yokohama                     City University Graduate School of Medicine, Yokohama 236‑0004, Japan.
authors.forename: Ryohei
authors.initials: R
authors.lastname: Takahashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Sato
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Klinman
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shimosato
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kaneko
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ishigatsubo
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000235:genetics; D017239:Paclitaxel / Q000008:administration & dosage; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D009838:Oligodeoxyribonucleotides; D003841:Deoxycytidine; D051057:Proto-Oncogene Proteins c-akt; D017239:Paclitaxel; D000093542:Gemcitabine