Suppressive oligodeoxynucleotides synergistically enhance antiproliferative effects of anticancer drugs in A549 human lung cancer cells.
Suppressive oligodeoxynucleotides synergistically enhance antiproliferative effects of anticancer drugs in A549 human lung cancer cells.
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DOI：
10.3892/ijo.2012.1755
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发表时间：
2013-02
影响因子：
5.2
通讯作者：
Ishigatsubo Y
中科院分区：
文献类型：
--
作者：
Takahashi R;Sato T;Klinman DM;Shimosato T;Kaneko T;Ishigatsubo Y
含有重复TTAGGG基序的免疫抑制寡核苷酸(Sup ODN)可以减轻炎症，因此可能对炎症相关的肿瘤生长产生影响。在这项研究中，我们发现与对照组相比，Sup ODN对A549非小细胞肺癌(NSCLC)细胞株具有显著的抑制增殖作用(p<；0.05)。Sup-ODN通过抑制Akt和细胞外信号调节激酶1/2的磷酸化以及p15INK4b和p27KIP1/视网膜母细胞瘤蛋白通路，使细胞周期停滞于G1期。此外，Sup ODns与长春瑞滨合用时可诱导细胞凋亡，并促进细胞凋亡。在类似于晚期非小细胞肺癌多药化疗的临床应用的情况下，通过将Sup ODN与传统抗癌药物联合使用来研究这些效果。Sup ODN与5-氟尿嘧啶、长春瑞滨、吉西他滨、紫杉醇和伊立替康有显著的协同作用，在A549 NSCLC细胞中的平均结合指数为0.43~0.78(<；1.0为协同作用)。综上所述，我们的结果表明，Sup ODN具有抗癌作用，并通过改变Akt和细胞外信号调节激酶1/2通路而增加NSCLC细胞对常规抗癌药物的敏感性。因此，Sup ODN可能成为非小细胞肺癌患者的一种新的治疗策略。
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 extra-cellular 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 extra-cellular signal-regulated kinase 1/2 pathway. Thus, Sup ODNs may serve as a novel therapeutic strategy for NSCLC patients.
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影响因子：
6.4
作者：
Longe, Harold O.;Romesser, Paul B.;Rankin, Andrew M.;Faller, Douglas V.;Eller, Mark S.;Gilchrest, Barbara A.;Denis, Gerald V.
通讯作者：
Denis, Gerald V.
影响因子：
45.3
作者：
Sandler, AB;Nemunaitis, J;Einhorn, LH
通讯作者：
Einhorn, LH
影响因子：
4.4
作者：
Gursel, I;Gursel, M;Klinman, DM
通讯作者：
Klinman, DM
影响因子：
158.5
作者：
Sandler, Alan;Gray, Robert;Johnson, David H.
通讯作者：
Johnson, David H.
影响因子：
3.3
作者：
Okamura, Mayumi;Yamaji, Satoshi;Ishigatsubo, Yoshiaki
通讯作者：
Ishigatsubo, Yoshiaki