机构:[1]Department of Rehabilitation Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China.四川大学华西医院[2]Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China.[3]Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu 610041, China.[4]Department of Basic Medical Sciences & Forensic Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.四川大学华西医院[5]Innovation Center of Nursing Research, Nursing Key Laboratory of Sichuan Province, West China Hospital, Chengdu 610041, China.四川大学华西医院[6]Key Laboratory of Rehabilitation Medicine in Sichuan Province/Rehabilitation Medicine Research Institute, Chengdu 610041, China.
The strategy of drug repurposing has gained traction in the field of cancer therapy as a means of discovering novel therapeutic uses for established pharmaceuticals. Paroxetine (PX), a selective serotonin reuptake inhibitor typically utilized in the treatment of depression, has demonstrated promise as an agent for combating cancer. Nevertheless, the specific functions and mechanisms by which PX operates in the context of triple-negative breast cancer (TNBC) remain ambiguous. This study aimed to examine the impact of PX on TNBC cells in vitro as both a standalone treatment and in conjunction with other pharmaceutical agents. Cell viability was measured using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, apoptosis was assessed through flow cytometry, and the effects on signaling pathways were analyzed using RNA sequencing and Western blot techniques. Furthermore, a subcutaneous tumor model was utilized to assess the in vivo efficacy of combination therapy on tumor growth. The results of our study suggest that PX may activate the Ca2+-dependent mitochondria-mediated intrinsic apoptosis pathway in TNBC by potentially influencing the PI3K/AKT/mTOR pathway as well as by inducing cytoprotective autophagy. Additionally, the combination of PX and chemotherapeutic agents demonstrated moderate inhibitory effects on 4T1 tumor growth in an in vivo model. These findings indicate that PX may exert its effects on TNBC through modulation of critical molecular pathways, offering important implications for improving chemosensitivity and identifying potential therapeutic combinations for clinical use.
基金:
Support Program of the Innovation Research Project from 0 to 1 (No. 2023SCUH0071), the Support Program of the Science and Technology Department of Sichuan Province (No. 2023YFSY0046), and the Department of Science and Technology of Sichuan Province (Grant No. 2022YFS0061).
语种:
外文
PubmedID:
中科院(CAS)分区:
出版当年[2024]版:
无
最新[2023]版:
大类|2 区医学
小类|3 区肿瘤学
第一作者:
第一作者机构:[1]Department of Rehabilitation Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China.
共同第一作者:
通讯作者:
通讯机构:[2]Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China.[3]Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu 610041, China.
推荐引用方式(GB/T 7714):
Huang Qianrui,Wu Mengling,Pu Yamin,et al.Inhibition of TNBC Cell Growth by Paroxetine: Induction of Apoptosis and Blockage of Autophagy Flux[J].Cancers.2024,16(5):doi:10.3390/cancers16050885.
APA:
Huang Qianrui,Wu Mengling,Pu Yamin,Zhou Junyou,Zhang Yiqian...&Ma Yimei.(2024).Inhibition of TNBC Cell Growth by Paroxetine: Induction of Apoptosis and Blockage of Autophagy Flux.Cancers,16,(5)
MLA:
Huang Qianrui,et al."Inhibition of TNBC Cell Growth by Paroxetine: Induction of Apoptosis and Blockage of Autophagy Flux".Cancers 16..5(2024)