Investigation on the determination of tumor-associated macrophages inducing the drug resistance of albumin-bound paclitaxel in triple-negative breast cancer cells by activating IGF-1R signaling pathway

doi:10.11958/20230438

Abstract

Abstract:

Objective To investigate the effect of tumor-associated macrophages (TAM) on the chemosensitivity of triple-negative breast cancer (TNBC) cells to albumin-bound paclitaxel (Nab-PTX). Methods TAM model was constructed and identified. TNBC cell line MDA-MB-231 was established by Transwell cell co-culture method. They were divided into the control group (MDA-MB-231 cells and blank chamber), the Nab-PTX group (MDA-MB-231 cells, blank chamber and 0.5 nmol/L Nab-PTX), the TAM group (MDA-MB-231 cells, containing M2-type macrophages), the TAM+Nab-PTX group (MDA-MB-231 cells, cells containing M2-type macrophages and 0.5 nmol/L Nab-PTX) and the insulin-like growth factor 1 receptor (IGF-1R) inhibitor group (MD-MB-231 cells, macrophage compartment containing M2-type, 0.5 nmol/L Nab-PTX and 4 nmol/L IGF-1R inhibitor Linsitinib). The cell survival rate of each group was determined by CCK-8 method. Flow cytometry was used to detect cell apoptosis. The mRNA levels of multidrug resistant protein (MDR) 1 and Caspase-3 were detected by real-time quantitative PCR (qPCR). The key proteins of IGF-1R signaling pathway were detected by Western blot assay. Results THP-1 cells were induced to differentiate into M2 macrophages. Compared with the Nab-PTX group, the cell proliferation rate was increased and apoptosis rate was decreased in the TAM+Nab-PTX group (P<0.01). The mRNA expression of MDR1was increased and Caspase-3 mRNA was decreased (P<0.05). The key protein of IGF-1R signaling pathway was activated (P<0.01). Compared with the TAM+Nab-PTX group, the proliferation rate was decreased and apoptosis rate of cells was increased in the IGF-1R inhibitor group. The mRNA expression of MDR1 was decreased, the mRNA expression of Caspase3 was increased, and the expression of key proteins in IGF-1R signaling pathway was decreased (P<0.01). Conclusion TAM may induce resistance of TNBC cells to Nab-PTX by activating IGF-1R signaling pathway.

Key words: tumor-associated macrophages, triple negative breast neoplasms, albumin-bound paclitaxel, drug tolerance, receptor, IGF type 1

CLC Number:

R737.9

Figures/Tables 10

References 19

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组别	24 h	48 h	72 h
对照组	0.470±0.002	0.630±0.001	0.770±0.004
Nab-PTX组	0.440±0.002^a	0.540±0.004^a	0.620±0.003^a
TAM组	0.510±0.002^b	0.720±0.001^b	0.930±0.006^b
TAM+Nab-PTX组	0.460±0.002^b	0.610±0.003^b	0.760±0.006^b
F	716.879^＊＊	2 090.309^＊＊	2 276.647^＊＊

组别	24 h	48 h	72 h
对照组	0.470±0.002	0.630±0.001	0.770±0.004
Nab-PTX组	0.440±0.002^a	0.540±0.004^a	0.620±0.003^a
TAM组	0.510±0.002^b	0.720±0.001^b	0.930±0.006^b
TAM+Nab-PTX组	0.460±0.002^b	0.610±0.003^b	0.760±0.006^b
F	716.879^＊＊	2 090.309^＊＊	2 276.647^＊＊

组别	24 h	48 h	72 h
TAM+Nab-PTX组	0.460±0.002	0.610±0.003	0.760±0.006
IGF-1R抑制剂组	0.420±0.001	0.500±0.003	0.560±0.003
t	19.290^＊＊	42.832^＊＊	45.987^＊＊

组别	24 h	48 h	72 h
TAM+Nab-PTX组	0.460±0.002	0.610±0.003	0.760±0.006
IGF-1R抑制剂组	0.420±0.001	0.500±0.003	0.560±0.003
t	19.290^＊＊	42.832^＊＊	45.987^＊＊

组别	MDR1	Caspase-3
对照组	1.00±0.03	1.00±0.02
Nab-PTX组	0.29±0.01^a	2.03±0.04^a
TAM组	1.72±0.61	0.58±0.40
TAM+Nab-PTX组	0.83±0.03^b	1.20±0.02^b
F	934.279^＊＊	21.360^＊＊