ABSTRACT
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/ß 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.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Humans , Becaplermin/metabolism , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Lung Neoplasms/pathology , Adenocarcinoma of Lung/pathology , Cell Transformation, Neoplastic/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Cell Movement/genetics , Cell Line, TumorABSTRACT
A field experiment with split-plot design was conducted to study the effects of watering, nitrogen fertilization, and their interactions on the growth, grain yield, and water- and nitrogen use efficiency of winter wheat. Four watering levels (0, 900, 1200, and 1500 m3 x hm(-2)) in main plots and five nitrogen fertilization levels (0, 90, 150, 210, and 270 kg N x hm(-2)) in sub-plots were designed. The results showed that the grain yield, nitrogen absorption, nitrogen use efficiency, and nitrogen productive efficiency of winter wheat increased with increasing level of watering, but the nitrogen use efficiency and nitrogen productive efficiency decreased with increasing nitrogen fertilization level. The grain yield, nitrogen absorption, and nitrogen harvest index were increased with increasing nitrogen fertilization level when the nitrogen application rate was 0-150 kg N x hm(-2), but not further increased significantly when the nitrogen application rate exceeded 150 kg x hm(-2). With the increasing level of watering, the water consumption amount (WCA) and the total water use efficiency increased, while the proportion of precipitation and soil water supply to WCA as well as the irrigation water use efficiency decreased. With the increasing level of nitrogen fertilization, the proportion of precipitation and watering amount to WCA increased, that of soil water supply to WCA decreased, and the total water use efficiency and irrigation water use efficiency decreased after an initial increase, with no significant differences among the treatments of 150, 210, and 270 kg N x hm(-2). It was considered that under our experimental condition, 1500 m3 x hm(-2) of watering amount plus 150 kg x hm(-2) of nitrogen fertilization could be the optimal combination for the high yielding and high efficiency.
