Mechanisms of tanshinone Ⅱ A promoting migration and invasion of breast cancer cells by regulating Hedgehog/Gli1 signaling pathway

Chen Yun-yun; Xu Bao-qin

doi:10.3969/j.issn.1672-8157.2024.03.022

Abstract：Objective To observe the mechanisms of tanshinone ⅡA(Tan ⅡA)for promoting migration and invasion of breast cancer cells.Methods After the breast cancer cell line MCF-7 was treated with different concentrations of Tan ⅡA,the cell viability was detected by MTT assay,apoptosis determined by flow cytometry and the migration and invasion of the cells determined by Transwell assay.The Hedgehog activator SAG was used to activate the Hedgehog/Gli1 pathway.The expression levels of mRNA and protein of SMO and Gli1 were detected by qRT-PCR and Western blot.The expression levels of autophagy-related proteins LC3-Ⅰ,LC3-Ⅱ and Beclin-1 were determined by Western blot.Results 50 μmol·L-1 Tan ⅡA significantly inhibited the activity of MCF-7 cells,the activity of MDA-MB-231 cells decreased from(98.12±3.85)%to(69.32±3.68)%,and the activity of MCF-7 cells decreased from(99.32±3.65)%to(49.65±3.74)%.The cell viability of MCF-7 was significantly increased to(71.20±5.00)%after SAG addition(P<0.05).SAG significantly inhibited apoptosis of MCF-7 cells,and the apoptosis rate decreased from(20.50±2.00)%to(12.00±1.00)%.SAG increased the number of MCF-7 cell migration from(52.00±5.00)to(76.00±5.00)(P<0.05),and the number of invasion from(41.00±3.00)to(75.00±5.00)(P<0.05).Compared with control group,Beclin-1 protein level in Tan ⅡA group was increased from(0.54±0.05)to(1.20±0.10),LC3-Ⅱ/LC3-Ⅰlevel was increased from(0.60±0.06)to(1.80±0.12)(P<0.05).After addition of SAG,Beclin-1 protein level was significantly decreased to(0.70±0.07)(P<0.05),LC3-Ⅱ/LC3-Ⅰlevel was significantly decreased to(0.75±0.04)(P<0.05).Conclusion Tan ⅡA can reduce the viability,migration and invasion of the breast cancer cells,inhibit the activity of Hedgehog/Gli1 signaling pathway,and promote the autophagy of the cells.