Hu F Q, Qiao T, Xie X, Hu R, Xiao H B
Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
J Biol Regul Homeost Agents. 2014 Oct-Dec;28(4):649-57.
Pentraxin-3 (PTX3), a modulator of tumor-associated inflammation, is known to be positively correlated with tumor grade and severity of malignancies, but the function and molecular underlying mechanisms of PTX3 remain unclear. In the present study, the expression of PTX3 in human lung adenocarcinoma (LAC) was examined by immunohistochemical assay using a tissue microarray procedure. A loss-of-function experiment was performed to explore the effects of lentiviral vector-mediated PTX3 shRNA (Lv-shPTX3) on cell growth and invasive potential in LAC cell lines (A549 and LETPα-2), assessed by MTT and Transwell assays, respectively. We found that the expression of PTX3 protein was significantly increased in LAC tissues compared with that in adjacent non-cancerous tissues (ANCT) (60.42% vs. 29.17%, P=0.004), and positively correlated with lymphatic invasion of the tumor (P=0.006). Furthermore, knockdown of PTX3 suppressed tumor proliferation and invasion of LAC cells, followed by decreased expression of p-AKT, p-NF-kappa B, PCNA, and MMP-9. Taken together, our findings demonstrate that upregulation of PTX3 expression is correlated with tumor metastasis of LAC patients, and knockdown of PTX3 blocks the development of LAC through inhibition of the AKT and NF-kappa B pathways, suggesting that PTX3 may serve as a potential therapeutic target for the treatment of cancer.
五聚体蛋白3（PTX3）是肿瘤相关炎症的调节因子，已知其与肿瘤分级和恶性肿瘤严重程度呈正相关，但PTX3的功能及分子机制仍不清楚。在本研究中，采用组织芯片技术通过免疫组化分析检测了PTX3在人肺腺癌（LAC）中的表达。进行了功能缺失实验，以探讨慢病毒载体介导的PTX3短发夹RNA（Lv-shPTX3）对LAC细胞系（A549和LETPα-2）细胞生长和侵袭潜能的影响，分别通过MTT和Transwell实验进行评估。我们发现，与相邻非癌组织（ANCT）相比，LAC组织中PTX3蛋白表达显著增加（60.42%对29.17%，P=0.004），且与肿瘤的淋巴侵袭呈正相关（P=0.006）。此外，PTX3基因敲低抑制了LAC细胞的肿瘤增殖和侵袭，随后p-AKT、p-NF-κB、PCNA和MMP-9的表达降低。综上所述，我们的研究结果表明，PTX3表达上调与LAC患者的肿瘤转移相关，PTX3基因敲低通过抑制AKT和NF-κB途径阻断LAC的发展，提示PTX3可能作为癌症治疗的潜在靶点。
