Feng Kai, Cai Xiaoping, Qiao Gaofeng
Department of Thoracic Surgery II, Binzhou People's Hospital, Binzhou, China.
Department of Oncology II, Binzhou People's Hospital, Binzhou, China.
Cytojournal. 2025 Mar 13;22:33. doi: 10.25259/Cytojournal_190_2024. eCollection 2025.
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.
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.
Elevated levels of PDGFB expression were markedly detected in various lung cancer cell lines, notably A549 and H460 ( < 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 ( < 0.001). Moreover, an association was found between increased levels of Ki67 expression and elevated PDGFB expression ( < 0.001). The upregulation of PDGFB was linked to heightened migratory ( < 0.001), invasive ( < 0.001), and proliferative ( < 0.001) capacities of the cells. Furthermore, an elevation in lactate levels and ECAR ( < 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.
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.
肺癌因其高发病率和死亡率，是一项严峻的全球健康挑战。代谢重编程，尤其是向有氧糖酵解的转变，通过维持肿瘤快速增殖所需的能量，在肺癌进展中起关键作用。血小板衍生生长因子亚基B（PDGFB）通过特定信号级联促进肺癌生长和转移，这一点已得到充分证实。然而，仍需进一步研究以阐明PDGFB在葡萄糖代谢中的复杂调控机制及其对肺癌进展的影响。我们的研究致力于探索PDGFB通过调节葡萄糖代谢对肺癌的影响。
首先，我们使用定量实时聚合酶链反应和蛋白质免疫印迹分析，确定PDGFB在各种肺癌细胞系（A549、H460、HCC827和H1975）中的表达模式。我们通过免疫组织化学测量肺癌患者肿瘤组织中PDGFB和Ki-67的表达水平。然后，我们用PDGFB过表达（PDGFB OE）质粒转染肺癌细胞。使用伤口愈合实验和Transwell实验评估PDGFB OE和半乳糖+PDGFB OE联合处理对细胞迁移和侵袭特性的影响。通过集落形成实验和5-乙炔基-2'-脱氧尿苷染色实验评估PDGFB OE和半乳糖+PDGFB OE联合处理对肺癌细胞增殖能力的影响。我们还使用细胞外酸化率（ECAR）测量方法，测量PDGFB OE对肺癌细胞线粒体功能和糖酵解能力的影响。
在各种肺癌细胞系中均明显检测到PDGFB表达水平升高，尤其是A549和H460（<0.001）。对肺癌患者肿瘤样本的分析验证了这一观察结果，这些患者的肿瘤组织中PDGFB表达升高（<0.001）。此外，发现Ki67表达水平升高与PDGFB表达升高之间存在关联（<0.001）。PDGFB的上调与细胞迁移（<0.001）、侵袭（<0.001）和增殖（<0.001）能力增强有关。此外，PDGFB OE组的乳酸水平和ECAR升高（<0.001），同时糖酵解相关调节蛋白水平增加。用半乳糖抑制有氧糖酵解有效减轻了PDGFB诱导的肺癌细胞增殖和迁移增强。
通过影响葡萄糖代谢，PDGFB驱动肺癌的生长和转移凸显了其作为这种复杂疾病治疗靶点的潜力。
