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杜松提取物在体内外诱导结直肠腺癌细胞周期停滞和凋亡。

Juniperus communis extract induces cell cycle arrest and apoptosis of colorectal adenocarcinoma in vitro and in vivo.

机构信息

Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Republic of China, Taiwan.

Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Republic of China, Taiwan.

出版信息

Braz J Med Biol Res. 2021 Jul 16;54(10):e10891. doi: 10.1590/1414-431X2020e10891. eCollection 2021.

Abstract

Juniperus communis (JCo) is a well-known traditional Chinese medicinal plant that has been used to treat wounds, fever, swelling, and rheumatism. However, the mechanism underlying the anticancer effect of JCo extract on colorectal cancer (CRC) has not yet been elucidated. This study investigated the anticancer effects of JCo extract in vitro and in vivo as well as the precise molecular mechanisms. Cell viability was evaluated using the MTT assay. Cell cycle distribution was examined by flow cytometry analysis, and cell apoptosis was determined by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Protein expression was analyzed using western blotting. The in vivo activity of the JCo extract was evaluated using a xenograft BALB/c mouse model. The tumors and organs were examined through hematoxylin-eosin (HE) staining and immunohistochemistry. The results showed that JCo extract exhibited higher cytotoxicity against CRC cells than against normal cells and showed synergistic effects when combined with 5-fluorouracil. JCo extract induced cell cycle arrest at the G0/G1 phase via regulation of p53/p21 and CDK4/cyclin D1 and induced cell apoptosis via the extrinsic (FasL/Fas/caspase-8) and intrinsic (Bax/Bcl-2/caspase-9) apoptotic pathways. In vivo studies revealed that JCo extract suppressed tumor growth through the inhibition of proliferation and induction of apoptosis. In addition, there was no obvious change in body weight or histological morphology of normal organs after treatment. JCo extract suppressed CRC progression by inducing cell cycle arrest and apoptosis in vitro and in vivo, suggesting the potential application of JCo extract in the treatment of CRC.

摘要

欧洲刺柏(Juniperus communis,JCo)是一种广为人知的传统中药,用于治疗创伤、发热、肿痛和风湿等病症。然而,JCo 提取物对结直肠癌(CRC)的抗癌作用机制尚未阐明。本研究从体外和体内水平研究了 JCo 提取物的抗癌作用及其确切的分子机制。采用 MTT 法评估细胞活力。通过流式细胞术分析检测细胞周期分布,通过末端脱氧核苷酸转移酶 dUTP 缺口末端标记(TUNEL)检测法测定细胞凋亡。采用 Western blot 分析蛋白表达。利用异种移植 BALB/c 小鼠模型评估 JCo 提取物的体内活性。通过苏木精-伊红(HE)染色和免疫组织化学检查肿瘤和器官。结果表明,JCo 提取物对 CRC 细胞的细胞毒性高于正常细胞,与 5-氟尿嘧啶联合使用时具有协同作用。JCo 提取物通过调节 p53/p21 和 CDK4/细胞周期蛋白 D1 将细胞周期阻滞在 G0/G1 期,并通过外源性(FasL/Fas/caspase-8)和内源性(Bax/Bcl-2/caspase-9)凋亡途径诱导细胞凋亡。体内研究表明,JCo 提取物通过抑制增殖和诱导凋亡抑制肿瘤生长。此外,治疗后正常器官的体重或组织形态学无明显变化。JCo 提取物通过诱导细胞周期阻滞和凋亡在体外和体内抑制 CRC 进展,表明 JCo 提取物在 CRC 治疗中的潜在应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3eb/8289341/d596e9b47a0a/1414-431X-bjmbr-54-10-e10891-gf001.jpg

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