Toxicol Appl Pharmacol. 2021 Jan 1;410:115336.doi: 10.1016/j.taap.2020.115336. Epub 2020 Nov 17.

Ligustilide inhibits the proliferation of non-small cell lung cancer via glycolytic metabolism

Xiufeng Jiang  1 Wei Zhao  2 Feng Zhu  2 Hui Wu  2 Xiao Ding  2 Jinmei Bai  2 Xiaoqing Zhang  2 Meifang Qian  2 Affiliations

Abstract

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related death worldwide. The abnormal activation of glycolytic metabolism and PTEN/AKT signaling in NSCLC cells are highly correlated with their proliferation abilities and viability. Ligustilide is one of the major bioactive components of multiple Chinese traditional medicine including Angelica sinensis and Ligusticum. Ligustilide exposure inhibits the proliferation and viability of multiple cancer cell lines in vitro. However, the impact of ligustilide to the progression of NSCLC and its detailed pharmacological mechanisms remain unclear. In this research, CCK-8 and colony formation assay were performed to demonstrate ligustilide treatment inhibited the viability and proliferation ability of NSCLC cells in vitro. Caspase-3/-7 activity assay and nucleosome ELISA assay were utilized to show ligustilide promoted the apoptosis of NSCLC cells. Metabolic analysis and qRT-PCR assay were used to demonstrated that ligustilide dampened aerobic glycolysis of NSCLC cells. Nude mice were exposed to 5 mg/kg ligustilide and ligustilide inhibited orthotopic NSCLC growth in vivo. qRT-PCR and Western blot analysis were performed to substantiate the regulatory function of ligustilide to PTEN/AKT signaling in NSCLC cells. Overall, this study revealed that ligustilide regulated the proliferation, apoptosis and aerobic glycolysis of NSCLC cells through PTEN/AKT signaling pathway.

Keywords: Glycolysis; Ligustilide; Non-small cell lung cancer; PTEN/AKT signaling.

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