In this study, isoliquiritigenin (ISL) incorporated nanoliposomes were prepared and their effects on colorectal cancer (CRC) cell lines were investigated. Herein, we sought to explore the anti-cancer mechanisms of ISL loaded nanoliposomes (ISL-NLs) on AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathways mediated glycolysis. Also, the key targets such as caveolin 1 (CAV1), glucose transporters and Akt/mTOR that promote glycolysis, and are activated via the induction of α-enolase (ENO1), fructose bisphosphate aldolase A (ALDOA) and monocarboxylate transporter 4 (MCT4) expressions were also investigated. It was shown that ISL-NLs significantly suppressed the proliferation and glucose uptake of CRC cell by potentially regulating the glycolysis and lactate targets as well as pathways that formed the basis of the anti-CRC effects of ISL-NLs. The mechanism underlying this effect was further validated via the regulation of some key targets such as ENO1, ALDOA, lactate dehydrogenase A (LDHA) and MCT4 in glycolysis coupled with cellular myelocytomatosis oncogene (c-myc), hypoxia-inducible factor 1-alpha (HIF-1α) in protein kinase B/mTOR (Akt/mTOR) pathways. Moreover, the AMPK proteins were identified to be up-regulated while the lactic acid production was suppressed by ISL-NLs in the CRC cells, indicating that ISL-NLs had an inhibitory effect on AMPK mediated glycolysis and lactate production. Altogether, these results have provided insights into the mechanism underlying the key role that liposomal ISL played in the multiple inhibition of AMPK and Akt/mTOR mediated glycolysis and lactate generation, which may be regulated as the alternative metabolic pathways of CRC as well as serve as adjuvant therapy for the disease.

中文翻译：

---

负载异甘草素的纳米脂质体调节 AMPK/mTOR 介导的结直肠癌糖酵解的作用和机制。

在这项研究中，制备了掺入异甘草素 (ISL) 的纳米脂质体，并研究了它们对结直肠癌 (CRC) 细胞系的影响。在此，我们试图探索负载 ISL 的纳米脂质体 (ISL-NL) 对 AMP 活化蛋白激酶/哺乳动物雷帕霉素靶标 (AMPK/mTOR) 通路介导的糖酵解的抗癌机制。此外，促进糖酵解并通过α-烯醇化酶 (ENO1)、果糖二磷酸醛缩酶 A (ALDOA) 和单羧酸转运蛋白 4 (MCT4) 的诱导激活的关键靶标，例如小窝蛋白 1 (CAV1)、葡萄糖转运蛋白和 Akt/mTOR ) 表达式也进行了调查。结果表明，ISL-NLs 通过潜在调节糖酵解和乳酸靶点以及形成 ISL-NLs 抗 CRC 作用基础的途径，显着抑制了 CRC 细胞的增殖和葡萄糖摄取。通过调节糖酵解中的一些关键目标，如 ENO1、ALDOA、乳酸脱氢酶 A (LDHA) 和 MCT4，以及细胞骨髓细胞瘤癌基因 (c-myc)、缺氧诱导因子 1-α，进一步验证了这种作用的机制。 HIF-1α) 在蛋白激酶 B/mTOR (Akt/mTOR) 通路中。此外，发现 AMPK 蛋白被上调，而乳酸产生被 CRC 细胞中的 ISL-NLs 抑制，表明 ISL-NLs 对 AMPK 介导的糖酵解和乳酸产生具有抑制作用。共，