Department of Immunology, Zunyi Medical College, Guizhou, China.
Immunol Lett. 2010 Jan 4;127(2):93-9. doi: 10.1016/j.imlet.2009.10.002. Epub 2009 Oct 23.
Accumulating data suggested that functional TLR9 was expressed in various tumor cells and TLR9 signaling could enhance the progression of tumor cells. However, the underlying mechanism of TLR9 signaling on the progression of tumors cells remains largely undefined. Our previous study demonstrated that the TLR9 agonist CpG ODNs could significantly enhance the progression of human lung cancer cells in vivo. Here we further evaluated the direct effect of CpG ODNs on the proliferation and cell cycle of human lung cancer cells. Our data showed that TLR9 agonist CpG ODNs could robustly elevate the proliferation and stimulate cell cycle entry of 95D cells in vitro, accompanied by the selectively up-regulated expression of CDK2. Furthermore, we found that down-regulation of CDK2 expression using siRNA against CDK2 could significantly inhibit the enhanced proliferation of 95D cells induced by CpG ODNs. Finally, we investigated that the CpG ODNs could selectively enhance the promoter activity of CDK2. Our findings indicated that TLR9 signaling could selectively up-regulate the expression of CDK2, which was critical for the enhanced proliferation of human lung cancer cells. Our results might provide novel insight into the understanding of functional expression of TLR9 on the progression of tumor cells.
有数据表明，功能性 TLR9 在各种肿瘤细胞中均有表达，TLR9 信号能促进肿瘤细胞的进展。然而，TLR9 信号促进肿瘤细胞进展的机制仍未完全阐明。我们先前的研究表明，TLR9 激动剂 CpG ODNs 能显著促进体内人肺癌细胞的进展。在此，我们进一步评估了 CpG ODNs 对人肺癌细胞增殖和细胞周期的直接影响。我们的数据表明，TLR9 激动剂 CpG ODNs 能显著增强 95D 细胞的体外增殖，并刺激细胞周期进入，同时选择性地上调 CDK2 的表达。此外，我们发现用针对 CDK2 的 siRNA 下调 CDK2 的表达能显著抑制 CpG ODNs 诱导的 95D 细胞增殖增强。最后，我们研究了 CpG ODNs 能选择性地增强 CDK2 启动子的活性。我们的研究结果表明，TLR9 信号能选择性地上调 CDK2 的表达，这对于人肺癌细胞的增殖增强至关重要。我们的研究结果可能为理解 TLR9 在肿瘤细胞进展中的功能表达提供新的见解。
