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辛伐他汀下调survivin 对唾液腺腺样囊性癌生长和侵袭的影响。

Effect of survivin downregulation by simvastatin on the growth and invasion of salivary adenoid cystic carcinoma.

机构信息

Department of Stomatology, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu 210008, P.R. China.

School of Pathology, Xuzhou Medical University, Xuzhou, Jiangsu 221000, P.R. China.

出版信息

Mol Med Rep. 2018 Aug;18(2):1939-1946. doi: 10.3892/mmr.2018.9204. Epub 2018 Jun 22.

DOI:10.3892/mmr.2018.9204
PMID:29956779
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6072162/
Abstract

Simvastatin, an inhibitor of 3‑hydroxy‑3-methylglutaryl‑coenzyme A reductase, is been used in the clinic due to its pleiotropic effects, such as breast cancer, prostate cancer, pancreatic cancer. Simvastatin has recently been demonstrated to serve a potential role in the prophylaxis and therapeutics of a number of human cancers. The majority of reports concerning simvastatin treatment in the majority of human cancers have demonstrated that survivin is significantly decreased as a result and has been implicated in tumorigenesis. However, only a limited number of studies have investigated the use of simvastatin for the treatment of salivary gland adenoid cystic carcinoma (SACC). Therefore, this agent is a candidate for further investigation. The aim of the present study was to investigate the effects of simvastatin on the proliferation, invasion and apoptosis of the human salivary adenoid cystic carcinoma cell line, SACC‑83, as well as survivin expression in the cells. The Cell Counting kit‑8 assay results revealed that simvastatin inhibited the proliferation of SACC‑83 cells in a dose‑dependent (10 to 50 µM) and time‑dependent (24 to 48 h) manner when compared with the untreated cells. Flow cytometry analysis indicated that simvastatin increased the percentage of cells in early and late apoptosis. Invasion assays revealed that simvastatin treatment inhibited the invasiveness of SACC‑83 cells in a dose‑dependent manner. In addition, simvastatin downregulated survivin expression in SACC‑83 cells. In conclusion, simvastatin significantly inhibited the proliferation and invasion of SACC‑83 cells, induced apoptosis, and reduced the expression of survivin, which suggests that simvastatin may be a novel target for SACC therapy.

摘要

辛伐他汀是 3-羟基-3-甲基戊二酰基辅酶 A 还原酶的抑制剂,由于其多种作用,如乳腺癌、前列腺癌、胰腺癌,已在临床上应用。辛伐他汀最近被证明在许多人类癌症的预防和治疗中具有潜在作用。大多数关于辛伐他汀治疗大多数人类癌症的报告表明,survivin 显著降低,并与肿瘤发生有关。然而,只有少数研究调查了辛伐他汀治疗涎腺腺样囊性癌 (SACC) 的用途。因此,该药物是进一步研究的候选药物。本研究旨在探讨辛伐他汀对人涎腺腺样囊性癌细胞系 SACC-83 的增殖、侵袭和凋亡以及细胞中 survivin 表达的影响。细胞计数试剂盒-8 检测结果显示,与未处理的细胞相比,辛伐他汀以剂量依赖性(10 至 50μM)和时间依赖性(24 至 48 小时)方式抑制 SACC-83 细胞的增殖。流式细胞术分析表明,辛伐他汀增加了早期和晚期凋亡细胞的百分比。侵袭实验表明,辛伐他汀以剂量依赖性方式抑制 SACC-83 细胞的侵袭能力。此外,辛伐他汀下调 SACC-83 细胞中 survivin 的表达。综上所述,辛伐他汀显著抑制 SACC-83 细胞的增殖和侵袭,诱导细胞凋亡,并降低 survivin 的表达,这表明辛伐他汀可能是 SACC 治疗的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f0a/6072162/85239c0a5b13/MMR-18-02-1939-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f0a/6072162/185424262c27/MMR-18-02-1939-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f0a/6072162/24f07f4cfe5d/MMR-18-02-1939-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f0a/6072162/28053ba09399/MMR-18-02-1939-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f0a/6072162/30fb23317afe/MMR-18-02-1939-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f0a/6072162/0c5f26a0e1e3/MMR-18-02-1939-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f0a/6072162/85239c0a5b13/MMR-18-02-1939-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f0a/6072162/185424262c27/MMR-18-02-1939-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f0a/6072162/24f07f4cfe5d/MMR-18-02-1939-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f0a/6072162/28053ba09399/MMR-18-02-1939-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f0a/6072162/30fb23317afe/MMR-18-02-1939-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f0a/6072162/0c5f26a0e1e3/MMR-18-02-1939-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f0a/6072162/85239c0a5b13/MMR-18-02-1939-g05.jpg

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