Abstract

Purpose

Pulsatilla saponins from pulsatilla chinensis (Bunge) Regel have potential anti-tumor activities to certain human cancers. However, the roles of pulsatilla saponin E separated from pulsatilla saponins in non-small cell lung cancer (NSCLC) have not been reported.

Materials and methods

After treating NSCLC cells by pulsatilla saponin E at different concentrations, cell viability was measured by MTT and CCK-8 assays, and cell migration, invasion and apoptosis were detected by scratch wound-healing, transwell and flow cytometry assays. The contents of free cholesterol (FC) and total cholesterol (TC) were measured by high performance liquid chromatography (HPLC). The expression levels of flotillin-1, flotillin-2, Akt, fatty acid synthase (FASN) were detected by qRT-PCR and Western blot assays.

Results

Pulsatilla saponin E suppressed viability, migration, invasion and promoted apoptosis of NSCLC cells followed by regulation of apoptosis-related proteins, reduced contents of FC and TC, and the expression levels of flotillin-1, flotillin-2, Akt, and FASN in a concentration-dependent manner. However, the inhibitory effects of pulsatilla saponin E on viability, migration, invasion of A549 cells and the expression levels of flotillin-1, flotillin-2, Akt, and FASN were reversed by flotillin-2 overexpression.

Conclusions

Our study revealed that pulsatilla saponin E suppressed migration, invasion and promoted apoptosis of NSCLC cells through negatively regulating Akt/FASN signaling pathway via the inhibition of flotillin-2 in lipid raft (LR). The current findings could be explored for developing a novel therapeutic drug for NSCLC treatment.

中文翻译：

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白头翁皂苷E通过抑制脂筏中的flotillin-2负调控Akt/FASN通路抑制NSCLC细胞的活力、迁移、侵袭并促进细胞凋亡

摘要

目的

来自白头翁 (Bunge) Regel的白头翁皂苷对某些人类癌症具有潜在的抗肿瘤活性。然而，从白头翁皂甙中分离出来的白头翁皂甙E在非小细胞肺癌（NSCLC）中的作用尚未见报道。

材料和方法

不同浓度白头翁皂苷E处理NSCLC细胞后，MTT和CCK-8检测细胞活力，划痕愈合、transwell和流式细胞仪检测细胞迁移、侵袭和凋亡。采用高效液相色谱法（HPLC）测定游离胆固醇（FC）和总胆固醇（TC）的含量。通过qRT-PCR和Western印迹法检测flotillin-1、flotillin-2、Akt、脂肪酸合酶(FASN)的表达水平。

结果

白头翁皂苷 E 抑制 NSCLC 细胞的活力、迁移、侵袭和促进凋亡，随后调节凋亡相关蛋白，降低 FC 和 TC 的含量，以及 flotillin-1、flotillin-2、Akt 和 FASN 的表达水平。浓度依赖性方式。然而，白头翁皂苷 E 对 A549 细胞的活力、迁移、侵袭以及 flotillin-1、flotillin-2、Akt 和 FASN 表达水平的抑制作用被 flotillin-2 过表达所逆转。

结论

我们的研究表明，白头翁皂苷E通过抑制脂筏（LR）中的flotillin-2负调控Akt/FASN信号通路来抑制NSCLC细胞的迁移、侵袭和促进凋亡。目前的研究结果可用于开发用于 NSCLC 治疗的新型治疗药物。