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油酸诱导舌鳞癌细胞凋亡和自噬的作用及机制

Oleic acid induces apoptosis and autophagy in the treatment of Tongue Squamous cell carcinomas.

机构信息

Department of Oral and Maxillofacial Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China.

Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi Province, 330006, China.

出版信息

Sci Rep. 2017 Sep 12;7(1):11277. doi: 10.1038/s41598-017-11842-5.

Abstract

Oleic acid (OA), a main ingredient of Brucea javanica oil (BJO), is widely known to have anticancer effects in many tumors. In this study, we investigated the anticancer effect of OA and its mechanism in tongue squamous cell carcinoma (TSCC). We found that OA effectively inhibited TSCC cell proliferation in a dose- and time-dependent manner. OA treatment in TSCC significantly induced cell cycle G0/G1 arrest, increased the proportion of apoptotic cells, decreased the expression of CyclinD1 and Bcl-2, and increased the expression of p53 and cleaved caspase-3. OA also obviously induced the formation of autolysosomes and decreased the expression of p62 and the ratio of LC3 I/LC3 II. The expression of p-Akt, p-mTOR, p-S6K, p-4E-BP1 and p-ERK1/2 was significantly decreased in TSCC cells after treatment with OA. Moreover, tumor growth was significantly inhibited after OA treatment in a xenograft mouse model. The above results indicate that OA has a potent anticancer effect in TSCC by inducing apoptosis and autophagy via blocking the Akt/mTOR pathway. Thus, OA is a potential TSCC drug that is worthy of further research and development.

摘要

油酸(OA)是鸦胆子油的主要成分之一,广泛用于多种肿瘤的抗癌作用。本研究旨在探讨 OA 在舌鳞癌细胞(TSCC)中的抗癌作用及其机制。结果表明,OA 能有效抑制 TSCC 细胞的增殖,且呈剂量和时间依赖性。OA 处理 TSCC 细胞可明显诱导细胞周期 G0/G1 期阻滞,增加细胞凋亡比例,降低 CyclinD1 和 Bcl-2 的表达,增加 p53 和 cleaved caspase-3 的表达。OA 还能明显诱导自噬溶酶体的形成,降低 p62 和 LC3 I/LC3 II 的比值。OA 处理后,TSCC 细胞中 p-Akt、p-mTOR、p-S6K、p-4E-BP1 和 p-ERK1/2 的表达明显降低。此外,OA 处理后在异种移植小鼠模型中肿瘤生长明显受到抑制。以上结果表明,OA 通过阻断 Akt/mTOR 通路诱导细胞凋亡和自噬,在 TSCC 中具有较强的抗癌作用。因此,OA 是一种有潜力的 TSCC 药物,值得进一步研究和开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b471/5595908/dcb805ea7241/41598_2017_11842_Fig1_HTML.jpg

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