Pirarubicin combined with TLR3 or TLR4 agonists enhances anti-tumor efficiency.

Autor: Zhang R; Central Laboratory, Hebei Collaborative Innovation Center of Tumor Microecological Metabolism Regulation, Affiliated Hospital of Hebei University, Baoding, 071000 Hebei, China; Clinical Medical College, Hebei University, Baoding, 071000 Hebei, China; Department of Breast Surgery, Affiliated Hospital of Hebei University, Baoding, 071000 Hebei, China., Cui NP; Department of Breast Surgery, Affiliated Hospital of Hebei University, Baoding, 071000 Hebei, China; Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Baoding, 071000 Hebei, China. Electronic address: cuinaipeng@hbu.edu.cn., He Y; Clinical Medical College, Hebei University, Baoding, 071000 Hebei, China; Department of Breast Surgery, Affiliated Hospital of Hebei University, Baoding, 071000 Hebei, China., Wang T; Central Laboratory, Hebei Collaborative Innovation Center of Tumor Microecological Metabolism Regulation, Affiliated Hospital of Hebei University, Baoding, 071000 Hebei, China; Clinical Medical College, Hebei University, Baoding, 071000 Hebei, China., Feng D; Clinical Medical College, Hebei University, Baoding, 071000 Hebei, China; Department of Breast Surgery, Affiliated Hospital of Hebei University, Baoding, 071000 Hebei, China., Wang Y; Department of Breast Surgery, Affiliated Hospital of Hebei University, Baoding, 071000 Hebei, China; Affiliated Hospital of Chongqing Medical University, Changshou People's Hospital, Changshou, 401220 Chongqing, China., Bao T; Clinical Medical College, Hebei University, Baoding, 071000 Hebei, China., Su C; Clinical Medical College, Hebei University, Baoding, 071000 Hebei, China., Qin Y; Central Laboratory, Hebei Collaborative Innovation Center of Tumor Microecological Metabolism Regulation, Affiliated Hospital of Hebei University, Baoding, 071000 Hebei, China., Shi JH; Central Laboratory, Hebei Collaborative Innovation Center of Tumor Microecological Metabolism Regulation, Affiliated Hospital of Hebei University, Baoding, 071000 Hebei, China; Clinical Medical College, Hebei University, Baoding, 071000 Hebei, China. Electronic address: shijianhong@hbu.edu.cn., Li JH; Department of Hepatobiliary Surgery, Affiliated Hospital of Hebei University, Baoding, 071000 Hebei, China; Hebei Key Laboratory of General Surgery for Digital Medicine, Baoding, 071000 Hebei, China. Electronic address: lijinghua@hbu.edu.cn.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Dec 05; Vol. 142 (Pt A), pp. 113068. Date of Electronic Publication: 2024 Sep 05.
DOI: 10.1016/j.intimp.2024.113068
Abstrakt: Background: Triple-negative breast cancer (TNBC) is prone to relapse due to the lack of effective therapeutic targets. Macrophages are the most abundant immune cells in the tumor microenvironment (TME) of breast cancer. Targeting the cross-talk between macrophages and cancer cells provides a more efficient strategy for anti-tumor therapy. Toll-like receptors (TLRs) are important players involved in macrophage activation, and TLR agonists are known to play roles in cancer therapy. However, the combination strategy of TLR agonists with chemotherapy drugs is still not well characterized.
Methods: RT-PCR and Western blot were used to detect the expression of TLRs. The communication between breast cancer cells and macrophages were determined by co-culture in vitro. Tumor cells proliferation and migration were investigated by MTT assay and scratch wound assay. The effects of drug combinations and toxic side effects were assessed by immunohistochemistry and Hematoxylin & Eosin staining.
Results: Expression of TLR3 and TLR4 were lower in breast tumor tissues compared with adjacent normal tissues. Patients with higher TLR3 or TLR4 expression levels had a better prognosis than those with lower expression levels. TLR3/4 expression was significantly inhibited when breast cancer cells MDA-MB-231 and E0771 were conditioned-cultured with macrophages in vitro and was also inhibited by pirarubicin (THP). However, the combination of TLR agonists and THP could reverse this response and inhibit the proliferation and migration of breast cancer cells. Additionally, this combination significantly reduced the tumor volume and weight in the murine model, increased the expression of TLR3/4 in mouse breast tumors.
Conclusions: Our results provide new ideas for the combination strategy of THP with TLR agonists which improves prognosis of breast cancer.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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