Investigation on the determination of tumor-associated macrophages inducing the drug resistance of human breast cancer

doi:10.3969/j.issn.1673-8640.2014.09.008

Abstract

Abstract:

Objective To investigate the role and drug resistance mechanism of tumor-associated macrophages (TAM) in human breast cancer cells. Methods Human monocytic cell line THP-1 was stimulated by phorbol myristate acetate (PMA), interleukin 4 (IL-4) and interleukin 13 (IL-13) to build a model of TAM which was cocultured with breast cancer cells in vitro. Flow cytometry (FCM) was used to determine CD14 and CD204. The effective concentration and time of paclitaxel for inhibiting the proliferation of breast cancer cell line T47D and BT-549, and the inhibitory rates of breast cancer cell cultured alone and cocultured with TAM/TAM conditioned medium were detected by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) colorimetric signal. The signal pathway change of phosphorylated signal transducers and activators of transduction 3 (p-STAT3) and phosphorylated c-Jun N-terminal kinase (p-JNK) were analyzed by Western Blot. Results THP-1 differentiated to TAM by PMA, IL-4 and IL-13 and showed the expressions of CD14 (31.52%±9.39%) and CD204 (48.21%±8.76%). Breast cancer cell lines which had been cocultured with TAM/TAM conditioned medium showed a significant increase in the number of survival cells compared to breast cancer cell lines cultured alone (T47D cultured alone:43.52%±9.40%, T47D cocultured: 92.68%±2.32%/92.20%±2.10%, BT-549 cultured alone: 63.08%±2.71%, BT-549 cocultured: 77.96%±2.64%/79.55%±2.35%, P<0.05). The apoptosis signal p-JNK was significantly down-regulated (P<0.05), and the p-STAT3 was up-regulated (P<0.05). Conclusions The model for TAM is established successfully. TAM protects breast cancer cells from the effect of paclitaxel through the secretion of cytokines which may caused by the activation of STAT3 and down regulation of p-JNK in tumor cells.

Key words: Tumor-associated macrophage, Breast cancer, Drug resistance, Paclitaxel

CLC Number:

R446.61

HE Linyan, YANG Cuixia, WANG Wenjuan, DU Yan, LIU Yiwen, HE Yiqing, GAO Feng. Investigation on the determination of tumor-associated macrophages inducing the drug resistance of human breast cancer[J]. , 2014, 29(9): 903-908.

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