Despite the countless therapeutic advances achieved over the years, non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. To this primacy contribute both non-oncogene addicted and advanced NSCLCs, in which conventional therapies are only partially effective. The adiponectin receptor agonist AdipoRon has revealed antiproliferative action in different cancers, including osteosarcoma and pancreatic cancer. Herein, we investigated its potential anticancer role in NSCLC for the first time. We proved that AdipoRon strongly inhibits viability, growth and colony formation in H1299 and A549 NSCLC cells, mainly through a slowdown in cell cycle progression. Along with the biological behaviors, a metabolic switching was observed after AdipoRon administration in NSCLC cells, consisting of higher glucose consumption and lactate accumulation. Remarkably, both 2-Deoxy Glucose and Oxamate glycolytic-interfering agents greatly enhanced AdipoRon’s antiproliferative features. As a master regulator of cell metabolism, AMP-activated protein kinase (AMPK) was activated by AdipoRon. Notably, the ablation of AdipoRon-induced AMPK phosphorylation by Compound-C significantly counteracted its effectiveness. However, the engagement of other pathways should be investigated afterwards. With a focus on NSCLC, our findings further support the ability of AdipoRon in acting as an anticancer molecule, driving its endorsement as a future candidate in NSCLC therapy.
尽管多年来取得了无数治疗进展，非小细胞肺癌（NSCLC）仍是全球癌症相关死亡的主要原因。这一主导地位既源于非致癌基因依赖型肺癌，也源于晚期非小细胞肺癌——对于这些病例，传统疗法仅能部分奏效。脂联素受体激动剂AdipoRon已在骨肉瘤和胰腺癌等多种癌症中显示出抗增殖作用。本研究首次探讨了其在非小细胞肺癌中的潜在抗癌作用。我们证实AdipoRon主要通过减缓细胞周期进程，显著抑制H1299和A549非小细胞肺癌细胞的活力、生长及集落形成能力。在生物学行为改变的同时，AdipoRon给药后非小细胞肺癌细胞出现代谢转换，表现为葡萄糖消耗增加和乳酸积累。值得注意的是，糖酵解干扰剂2-脱氧葡萄糖和草氨酸均能显著增强AdipoRon的抗增殖特性。作为细胞代谢的核心调控因子，AMP活化蛋白激酶（AMPK）被AdipoRon激活。特别需要指出的是，化合物C对AdipoRon诱导的AMPK磷酸化的消除作用显著削弱了其抗癌效果。然而，其他信号通路的参与机制仍有待后续研究。聚焦于非小细胞肺癌，我们的研究结果进一步证实了AdipoRon作为抗癌分子的潜力，为其成为未来非小细胞肺癌治疗的候选药物提供了理论依据。
肿瘤(癌症)患者之家