2. Academic Validation
  3. Thioridazine combined with carboplatin results in synergistic inhibition of triple negative breast cancer by targeting cancer stem cells

Thioridazine combined with carboplatin results in synergistic inhibition of triple negative breast cancer by targeting cancer stem cells

  • Transl Oncol. 2022 Sep 30;26:101549. doi: 10.1016/j.tranon.2022.101549.
Yi Wang 1,  Leiming Xia 2,  Jing Lin 1,  Li Gong 3,  Yang Xia 4,  Yang Xu 1,  Liu Liu 1,  Jian Bao 1,  Congshu Zhang 1,  Yuqing Chai 1,  Hongxia Li 5
Affiliations

Affiliations

  • 1 Department of Oncology, The First People's Hospital of Hefei/The Third Affiliated Hospital of Anhui Medical University, Hefei 230061, Anhui, PR China.
  • 2 Department of Hematopathology, The Fourth Affiliated Hospital of Anhui Medical University, Hefei 230002, Anhui, PR China.
  • 3 Department of Oncology, East District of First Affiliated Hospital of Anhui Medical University, Hefei 231600, Anhui, PR China.
  • 4 Department of Oncology, Taizhou People's Hospital/The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou 225300, Jiangsu, PR China.
  • 5 Department of Oncology, The First People's Hospital of Hefei/The Third Affiliated Hospital of Anhui Medical University, Hefei 230061, Anhui, PR China. Electronic address: lihongxia_dr@163.com.
PMID: 36191461 DOI: 10.1016/j.tranon.2022.101549
Abstract

Cancer Stem Cells (CSCs) in triple-negative breast Cancer (TNBC) are closely related to tumorigenesis and metastasis. Thioridazine (THZ) is a usual phenothiazine antipsychotic drug that can destroy CSCs. We aimed to explore whether THZ could sensitize metastatic TNBC cells, especially the CSCs, to carboplatin (CBP) treatment. Metastatic TNBC cells, 4T1 cells, and tumor-bearing mice were treated with THZ and CBP as monotherapy or combination therapy. MTT, flow cytometry, electron microscopy, immunohistochemistry and western blotting were applied to assess the cell viability, Apoptosis, mitochondrial morphology and the relevant protein levels, respectively. Tumor size and lung metastasis under different treatments as well as tumorigenesis of residual tumor cells from each group were monitored. THZ combined with CBP inhibited 4T1 tumor cell proliferation and induced Apoptosis by inhibiting the PI3K-AKT-mTOR pathway and activating Estrogen Receptor stress. THZ also showed strong activity against breast CSCs, THZ combined with CBP significantly destroyed Cancer cells, inhibited lung metastasis and relieved the tumor burden; Our data demonstrated that THZ can sensitize TNBC cells to CBP treatment and this combination therapy may provide a bright strategy for TNBC treatment by targeting both Cancer cells and CSCs.

Keywords

Cancer stem cells; Carboplatin; Lung metastasis; Synergistic inhibition; Thioridazine.

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