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伊维菌素与调制式电过热疗法协同作用，增强其在三阴性乳腺癌小鼠模型中的抗癌效果。

Ivermectin Synergizes with Modulated Electro-hyperthermia and Improves Its Anticancer Effects in a Triple-Negative Breast Cancer Mouse Model.

作者信息

Aloss Kenan, Leroy Viana Pedro Henrique, Bokhari Syeda Mahak Zahra, Giunashvili Nino, Schvarcz Csaba András, Bócsi Dániel, Koós Zoltán, Benyó Zoltán, Hamar Péter

机构信息

Institute of Translational Medicine, Semmelweis University, Üllői út 26., Budapest 1085, Hungary.

Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest 1089, Hungary.

出版信息

ACS Pharmacol Transl Sci. 2024 Jul 17;7(8):2496-2506. doi: 10.1021/acsptsci.4c00314. eCollection 2024 Aug 9.

DOI:10.1021/acsptsci.4c00314
PMID:39144564
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11320741/
Abstract

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, with limited treatment options. Modulated electro-hyperthermia (mEHT) is a novel adjuvant cancer therapy that induces selective cancer damage. However, mEHT upregulates heat shock protein beta 1 (HSPB1), a cancer-promoting stress chaperone molecule. Thus, we investigated whether ivermectin (IVM), an anthelmintic drug, may synergize with mEHT and enhance its anticancer effects by inhibiting HSPB1 phosphorylation. Isogenic 4T1 TNBC cells were inoculated into BALB/c mice and treated with mEHT, IVM, or a combination of both. IVM synergistically improved the tumor growth inhibition achieved by mEHT. Moreover, IVM downregulated mEHT-induced HSPB1 phosphorylation. Thus, the strongest cancer tissue damage was observed in the mEHT + IVM-treated tumors, coupled with the strongest apoptosis induction and proliferation inhibition. In addition, there was no significant body weight loss in mice treated with mEHT and IVM, indicating that this combination was well-tolerated. In conclusion, mEHT combined with IVM is a new, effective, and safe option for the treatment of TNBC.

摘要

三阴性乳腺癌（TNBC）是最具侵袭性的乳腺癌亚型，治疗选择有限。调制式电 hyperthermia（mEHT）是一种新型辅助癌症治疗方法，可诱导选择性癌症损伤。然而，mEHT 会上调热休克蛋白β1（HSPB1），这是一种促进癌症的应激伴侣分子。因此，我们研究了驱虫药伊维菌素（IVM）是否可与 mEHT 协同作用，并通过抑制 HSPB1 磷酸化来增强其抗癌效果。将同基因 4T1 TNBC 细胞接种到 BALB/c 小鼠体内，并用 mEHT、IVM 或两者组合进行治疗。IVM 协同增强了 mEHT 对肿瘤生长的抑制作用。此外，IVM 下调了 mEHT 诱导的 HSPB1 磷酸化。因此，在接受 mEHT + IVM 治疗的肿瘤中观察到最强的癌组织损伤，同时凋亡诱导和增殖抑制作用也最强。此外，接受 mEHT 和 IVM 治疗的小鼠体重没有显著减轻，表明这种联合治疗耐受性良好。总之，mEHT 联合 IVM 是治疗 TNBC 的一种新的、有效且安全的选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d033/11320741/abc48bd3bfae/pt4c00314_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d033/11320741/b93606d9dccf/pt4c00314_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d033/11320741/2706e2fdec8f/pt4c00314_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d033/11320741/3bb34dc1dd9e/pt4c00314_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d033/11320741/bfadb8eb11a7/pt4c00314_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d033/11320741/dd5cd0116fd6/pt4c00314_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d033/11320741/f8c5f9a54f80/pt4c00314_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d033/11320741/abc48bd3bfae/pt4c00314_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d033/11320741/b93606d9dccf/pt4c00314_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d033/11320741/2706e2fdec8f/pt4c00314_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d033/11320741/3bb34dc1dd9e/pt4c00314_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d033/11320741/bfadb8eb11a7/pt4c00314_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d033/11320741/dd5cd0116fd6/pt4c00314_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d033/11320741/f8c5f9a54f80/pt4c00314_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d033/11320741/abc48bd3bfae/pt4c00314_0007.jpg

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本文引用的文献

[1]
Augmentation of the EPR effect by mild hyperthermia to improve nanoparticle delivery to the tumor.

Biochim Biophys Acta Rev Cancer. 2024-7

[2]
Heat shock factor 1 inhibition enhances the effects of modulated electro hyperthermia in a triple negative breast cancer mouse model.

Sci Rep. 2024-4-8

[3]
Modulated Electro-Hyperthermia Accelerates Tumor Delivery and Improves Anticancer Activity of Doxorubicin Encapsulated in Lyso-Thermosensitive Liposomes in 4T1-Tumor-Bearing Mice.

Int J Mol Sci. 2024-3-7

[4]
Digoxin-Mediated Inhibition of Potential Hypoxia-Related Angiogenic Repair in Modulated Electro-Hyperthermia (mEHT)-Treated Murine Triple-Negative Breast Cancer Model.

ACS Pharmacol Transl Sci. 2024-1-9

[5]
Enhancing therapeutic efficacy in triple-negative breast cancer and melanoma: synergistic effects of modulated electro-hyperthermia (mEHT) with NSAIDs especially COX-2 inhibition in in vivo models.

Mol Oncol. 2024-4

[6]
Targeting the heat shock response induced by modulated electro-hyperthermia (mEHT) in cancer.

Biochim Biophys Acta Rev Cancer. 2024-3

[7]
The Clinical Validation of Modulated Electro-Hyperthermia (mEHT).

Cancers (Basel). 2023-9-15

[8]
High HSPB1 expression predicts poor clinical outcomes and correlates with breast cancer metastasis.

BMC Cancer. 2023-6-3

[9]
Recent Preclinical and Clinical Progress in Liposomal Doxorubicin.

Pharmaceutics. 2023-3-9

[10]
Is the antiparasitic drug ivermectin a suitable candidate for the treatment of epilepsy?

Epilepsia. 2023-3

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