Open AccessProteomic Level Changes on Treatment in MCF-7/DDP Breast Cancer Drug- Resistant Cells
Author(s) -
Gongshen Jin,
Kangwei Wang,
Yonghong Liu,
Xianhu Liu,
Xiaojing Zhang,
Hao Zhang
Publication year - 2020
Publication title -
anti-cancer agents in medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.508
H-Index - 96
eISSN - 1875-5992
pISSN - 1871-5206
DOI - 10.2174/1871520620666200213102849
Subject(s) - inhibitor of apoptosis , breast cancer , cancer research , apoptosis , cancer , medicine , cancer cell , caspase , programmed cell death , biology , biochemistry
Background: LCL161, a SMAC’S small molecule mimetic, can bind to a variety of IAPs and activateCaspases. We found that on its own, LCL161induces apoptosis of drug-resistant breast cancer cells bybinding to a variety of IAPs and activating Caspases. However, when LCL161 is used in combination withCaspase Inhibitors (CI), its capacity to induce apoptosis of breast cancer cells is enhanced. Objective: To carry out proteomic and bioinformatics analysis of LCL161 in combination with CI. We aim toidentify the key proteins and mechanisms of breast cancer drug-resistant apoptosis, thereby aiding in the breastcancer drug resistance treatment and identification of drug targeting markers. Methods: Cell culture experiments were carried out to explore the effect of LCL161 combined with CI on theproliferation of breast cancer drug-resistant cells. Proteomic analysis was carried out to determine the proteinexpression differences between breast cancer drug-resistant cells and LCL161 combined with CI treated cells.Bioinformatics analysis was carried out to determine its mechanism of action. Validation of proteomics resultswas done using Parallel Reaction Monitoring (PRM). Results: Cell culture experiments showed that LCL161 in combination with CI can significantly promote theapoptosis of breast cancer drug-resistant cells. Up-regulation of 92 proteins and down-regulation of 114 proteinsprotein were noted, of which 4 were selected for further validation. Conclusion: Our results show that LCL161 combined with CI can promote the apoptosis of drug-resistant breastcancer cells by down-regulation of RRM2, CDK4, and ITGB1 expression through Cancer pathways, p53 orPI3K-AKT signaling pathway. In addition, the expression of CDK4, RRM2, and CDC20 can be down-regulatedby the nuclear receptor pathway to affect DNA transcription and replication, thereby promoting apoptosis ofbreast cancer drug-resistant cells.