10.6084/M9.FIGSHARE.13374765
Yanlin Song
Yanlin
Song
Lu Li
Lu
Li
Jiao Chen
Jiao
Chen
Hongli Chen
Hongli
Chen
Bomiao Cui
Bomiao
Cui
Yun Feng
Yun
Feng
Ping Zhang
Ping
Zhang
Qiangsheng Zhang
Qiangsheng
Zhang
Yong Xia
Yong
Xia
Min Luo
Min
Luo
Thioridazine hydrochloride: an antipsychotic agent that inhibits tumor growth and lung metastasis in triple-negative breast cancer via inducing G0/G1 arrest and apoptosis
<p>Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer and still lacks available targeted therapy options. Thioridazine hydrochloride (Thi-hyd), a common phenothiazine antipsychotic drug, has shown great tumor-suppressive potential in several types of cancer cells. In this study, we explored the anti-tumor effects of Thi-hyd on TNBC. Thi-hyd significantly inhibited the viability and migration of TNBC cells <i>in vitro</i>. PI3K/AKT signaling pathway was verified to be related to Thi-hyd-induced tumor inhibition. G0/G1 cell cycle arrest and apoptosis were observed after treatment with Thi-hyd. The cell cycle arrest was accompanied by down-regulation of CDK4/cyclin D1 and up-regulation of p21 and p27. The apoptosis was accompanied by mitochondrial dysfunction. <i>In vivo</i>, Thi-hyd significantly suppressed the growth of tumors showing a 63.73% inhibition rate in tumor weight. Spontaneous lung metastasis was also efficiently prevented by Thi-hyd treatment, with a 72.58% inhibition rate. Immunohistological analysis showed increased Ki67 expression and reduced cleaved caspase-3 expression in Thi-hyd-treated mice. No apparent side effects were observed according to blood test and H&E staining results. Collectively, our results show that Thi-hyd can be used as a potential drug for TNBC treatment and set the basis for its clinical evaluation and investigation.</p> <p>CCK8: Cell Counting Kit-8; CDK: cyclin-dependent kinase; DRD2: dopamine D2 receptor; ERK1/2: extracellular signal-regulated kinase 1/2; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; H&E: hematoxylin and eosin; MMP: membrane potential; NAC: N-acetyl-L-cysteine; PI: Propidium iodide; Rh123: rhodamine-123; ROS: reactive oxygen species; TBST: tris-buffered saline containing 0.1% Tween 20 TNBC: Triple-negative breast cancer; Thi-hyd: Thioridazine hydrochloride.</p>
Biochemistry
Cell Biology
Molecular Biology
Pharmacology
Biotechnology
Developmental Biology
Cancer
Taylor & Francis
2020
2020-12-14
2023-05-31
Journal contribution
964682 Bytes
10.1080/15384101.2020.1850969
CC BY 4.0