Platelet-derived growth factor subunit B overexpression promotes lung cancer tumor growth and metastasis: The role of glucose metabolism.

Abstract

Objective: Lung cancer represents a formidable global health challenge due to its substantial prevalence and mortality rates. Metabolic reprogramming, especially the transition to aerobic glycolysis, plays a pivotal role in the progression of lung cancer by sustaining the energy demands for rapid tumor proliferation. The prominent involvement of platelet-derived growth factor subunit B (PDGFB) in promoting the growth and metastasis of lung cancer through specific signaling cascades is well established in. Nonetheless, further research is imperative to elucidate the intricate regulatory mechanisms of PDGFB in glucose metabolism and its implications for the advancement of lung cancer. Our study is dedicated to exploring the effect of PDGFB on lung cancer by modulating glucose metabolism.

Material and methods: First, we determined the expression patterns of PDGFB in various lung cancer cell lines (A549, H460, HCC827, and H1975) using quantitative real-time polymerase chain reaction and Western blot analyses. We measured the expression levels of PDGFB and Ki-67 in tumor tissues from lung cancer patients through immunohistochemistry. We then transfected lung cancer cells with a PDGFB overexpression (PDGFB OE) plasmid. The effects of PDGFB OE and galactose + PDGFB OE co-treatment on cell migration and invasion characteristics were assessed using wound healing and Transwell assays. The impact of PDGFB OE and galactose + PDGFB OE co-treatment on the proliferation capacity of lung cancer cells was evaluated through colony formation and 5-ethynyl-2'-deoxyuridine staining assays. We also measured the effects of PDGFB OE on mitochondrial function and glycolytic capacity in lung cancer cells using extracellular acidification rate assay (ECAR) measurement methods.

Results: Elevated levels of PDGFB expression were markedly detected in various lung cancer cell lines, notably A549 and H460 (P < 0.001). This observation was validated by the analysis of tumor samples from patients with lung cancer who exhibited heightened PDGFB expression in tumor tissues (P < 0.001). Moreover, an association was found between increased levels of Ki67 expression and elevated PDGFB expression (P < 0.001). The upregulation of PDGFB was linked to heightened migratory (P < 0.001), invasive (P < 0.001), and proliferative (P < 0.001) capacities of the cells. Furthermore, an elevation in lactate levels and ECAR (P < 0.001) was noted in the PDGFB OE group, along with increased levels of glycolysis-related regulatory proteins. The inhibition of aerobic glycolysis with galactose effectively mitigated the PDGFB-induced enhancement of lung cancer cell proliferation and migration.

Conclusion: By affecting glucose metabolism, PDGFB drives the growth and metastasis of lung cancer, underscoring its potential as a promising therapeutic target for the management of this complex disease.