Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.
Institute of Neurological Disease, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
Sci Rep. 2024 Feb 20;14(1):4191. doi: 10.1038/s41598-024-54801-7.
Lung adenocarcinoma (LUAD) remains one of the most aggressive tumors and the efficacy of conventional treatment has been bleak. Nowadays, gene-targeted therapy has become a new favorite in tumor therapy. Herein, we investigated the effect of platelet derived growth factor BB (PDGFBB) on LUAD. Firstly, PDGFBB was upregulated in LUAD patients and closely linked with poor survival. Furthermore, the expression of PDGFBB and PDGFRα/β in LUAD cells was higher than that in normal lung cells. By loss-of-function with herpes simplex virus (HSV)-PDGFi-shRNA, we found that PDGFBB knockdown caused a significant decrease in proliferation and migration, but evoked apoptosis of LUAD cells in vitro. Conversely, exogenous PDGFBB held adverse effect. Additionally, A549 cells with PDGFBB knockdown had a low probability of tumorigenesis in vivo. Moreover, PDGFBB knockdown restrained the growth of xenografts derived from normal A549 cells. Mechanistically, PDGFBB knockdown suppressed PI3K/AKT and Ras/MAPK signaling, while PDGFBB was the opposite. Therefore, we concluded that PDGFBB might facilitate the tumorigenesis and malignancy of LUAD through its functional downstream nodes-PI3K/AKT and Ras/MAPK signaling, which supported that PDGFBB could serve as a rational therapeutic target for LUAD.
肺腺癌（LUAD）仍然是最具侵袭性的肿瘤之一，常规治疗的疗效并不理想。如今，基因靶向治疗已成为肿瘤治疗的新宠。在这里，我们研究了血小板衍生生长因子 BB（PDGFBB）对 LUAD 的影响。首先，PDGFBB 在 LUAD 患者中上调，并与不良预后密切相关。此外，LUAD 细胞中 PDGFBB 和 PDGFRα/β的表达高于正常肺细胞。通过单纯疱疹病毒（HSV）-PDGFi-shRNA 的功能丧失，我们发现 PDGFBB 敲低导致 LUAD 细胞体外增殖和迁移显著减少，但诱发细胞凋亡。相反，外源性 PDGFBB 则产生不良影响。此外，PDGFBB 敲低的 A549 细胞在体内成瘤的可能性较低。此外，PDGFBB 敲低抑制了源自正常 A549 细胞的异种移植物的生长。从机制上讲，PDGFBB 敲低抑制了 PI3K/AKT 和 Ras/MAPK 信号通路，而 PDGFBB 则相反。因此，我们得出结论，PDGFBB 可能通过其功能下游节点 PI3K/AKT 和 Ras/MAPK 信号通路促进 LUAD 的肿瘤发生和恶性转化，这支持 PDGFBB 可以作为 LUAD 的合理治疗靶点。
