Department of Surgery, Shanghai Tongren Hospital, Shanghai 200336, P.R. China.
Department of Clinical Laboratory, Shanghai Tongren Hospital, Shanghai 200336, P.R. China.
Mol Med Rep. 2020 Feb;21(2):945-952. doi: 10.3892/mmr.2019.10855. Epub 2019 Nov 29.
Pancreatic cancer (PC) is the fourth leading cause of cancer‑related mortality worldwide. Leptin is an adipokine that is significantly increased in obese patients and that functions in various biological processes of cancer, such as tumor growth and metastasis. However, its role in PC cell proliferation and glucose metabolism and the underlying mechanisms remain unclear. In the present study, in vitro leptin treatment significantly promoted cell proliferation and increased glucose uptake and lactate production of human PC and healthy pancreas cells in a dose‑dependent manner, accompanied by increased expression of the glycolytic enzymes hexokinase II and glucose transporter 1. Furthermore, leptin receptor‑specific short hairpin RNAs were used to silence leptin receptor expression in PC cells, which had the opposite effect to leptin stimulation and decreased AKT phosphorylation. In addition, the effects of leptin stimulation were significantly counteracted by the AKT inhibitor LY294002, whereas the effects of leptin silencing were counteracted by AKT activator insulin‑like growth factor 1. The results of the present study suggested that leptin may contribute to cell proliferation and glucose metabolism of human PC cells, which may be through activation of the AKT pathway.
胰腺癌（PC）是全球癌症相关死亡的第四大主要原因。瘦素是一种脂肪细胞因子，在肥胖患者中显著增加，并且在癌症的各种生物学过程中发挥作用，例如肿瘤生长和转移。然而，其在 PC 细胞增殖和葡萄糖代谢中的作用及其潜在机制尚不清楚。在本研究中，体外瘦素处理以剂量依赖性方式显著促进人 PC 和健康胰腺细胞的增殖，并增加葡萄糖摄取和乳酸生成，同时伴随糖酵解酶己糖激酶 II 和葡萄糖转运蛋白 1 的表达增加。此外，使用瘦素受体特异性短发夹 RNA 沉默 PC 细胞中的瘦素受体表达，其作用与瘦素刺激相反，降低 AKT 磷酸化。此外，AKT 抑制剂 LY294002 显著拮抗瘦素刺激的作用，而 AKT 激活剂胰岛素样生长因子 1 拮抗瘦素沉默的作用。本研究结果表明，瘦素可能有助于人 PC 细胞的增殖和葡萄糖代谢，这可能是通过激活 AKT 通路。
