Kafeel Sanober, Ragone Angela, Salzillo Alessia, Palmiero Giuseppina, Naviglio Silvio, Sapio Luigi
Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.
Cancers (Basel). 2024 Jul 24;16(15):2633. doi: 10.3390/cancers16152633.
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，但非小细胞肺癌（NSCLC）仍是全球癌症相关死亡的主要原因。非致癌基因成瘾型和晚期NSCLC均导致了这一首要地位，在这些类型中，传统疗法仅部分有效。脂联素受体激动剂AdipoRon已在包括骨肉瘤和胰腺癌在内的不同癌症中显示出抗增殖作用。在此，我们首次研究了其在NSCLC中的潜在抗癌作用。我们证明，AdipoRon主要通过减缓细胞周期进程，强烈抑制H1299和A549 NSCLC细胞的活力、生长和集落形成。除了生物学行为外，在NSCLC细胞中给予AdipoRon后还观察到代谢转换，表现为更高的葡萄糖消耗和乳酸积累。值得注意的是，2-脱氧葡萄糖和草氨酸这两种糖酵解干扰剂都大大增强了AdipoRon的抗增殖特性。作为细胞代谢的主要调节因子，AMP激活的蛋白激酶（AMPK）被AdipoRon激活。值得注意的是，用化合物C消除AdipoRon诱导的AMPK磷酸化显著抵消了其有效性。然而，其他途径的参与情况随后应进行研究。聚焦于NSCLC，我们的研究结果进一步支持了AdipoRon作为抗癌分子的能力，促使其被认可为NSCLC治疗的未来候选药物。
