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抗精神病药物塞汀多通过抑制人胃癌细胞中的STAT3信号通路表现出抗增殖活性。

The Antipsychotic Agent Sertindole Exhibited Antiproliferative Activities by Inhibiting the STAT3 Signaling Pathway in Human Gastric Cancer Cells.

作者信息

Dai Chunyan, Liu Pei, Wang Xi, Yin Yifei, Jin Weiyang, Shen Li, Chen Yuzong, Chen Zhe, Wang Yiping

机构信息

Digestive Pathophysiology of Zhejiang Province, the First Affiliated Hospital of Zhejiang Chinese Medical University, 54 Youdian Road, Hangzhou, 310006, China.

College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, 310006, China.

出版信息

J Cancer. 2020 Jan 1;11(4):849-857. doi: 10.7150/jca.34847. eCollection 2020.

Abstract

Gastric cancer (GC) is the third leading cause of cancer-related death. Although the therapeutic approaches have improved, the 5-year survival rate of GC patients after surgical resection remains low due to the high rates of metastasis and recurrence. Patients with schizophrenia have significantly lower incidences of cancer after long-term drug treatment, suggesting the potential or partially ameliorate the risk of cancer development of antipsychotic drugs. The goal of this study was to explore antipsychotic drugs with an optional effective therapy against gastric cellular carcinoma. We found that sertindole, an atypical antipsychotic, exhibited anti-tumor efficacy on human GC cells and . Moreover, sertindole in combination with cisplatin dramatically enhanced apoptosis-induction in GC cells. In addition, the pro-apoptotic effect of sertindole on GC might in part, involved in inhibition of STAT3 activation and downstream signals, including Mcl1, surviving, c-Myc, cyclin D1. Collectively, these results suggested that sertindole could be a potential anticancer reagent and be an attractive therapeutic adjuvant for the treatment of human GC.

摘要

胃癌(GC)是癌症相关死亡的第三大主要原因。尽管治疗方法有所改进,但由于转移和复发率高,胃癌患者手术切除后的5年生存率仍然很低。长期药物治疗后,精神分裂症患者的癌症发病率显著降低,这表明抗精神病药物具有潜在的或部分改善癌症发生风险的作用。本研究的目的是探索对抗胃细胞癌具有选择性有效治疗作用的抗精神病药物。我们发现,非典型抗精神病药物舍吲哚对人胃癌细胞具有抗肿瘤功效。此外,舍吲哚与顺铂联合使用可显著增强胃癌细胞的凋亡诱导作用。此外,舍吲哚对胃癌的促凋亡作用可能部分涉及抑制信号转导和转录激活因子3(STAT3)的激活及其下游信号,包括髓细胞白血病-1(Mcl1)、生存素、原癌基因c-Myc、细胞周期蛋白D1。总体而言,这些结果表明舍吲哚可能是一种潜在的抗癌试剂,并且是治疗人类胃癌的一种有吸引力的治疗辅助药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92d5/6959018/101516663f7d/jcav11p0849g001.jpg

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