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西红花酸对人食管鳞状细胞癌KYSE - 150细胞的抗癌作用。

Anticancer effects of crocetin in human esophageal squamous cell carcinoma KYSE-150 cells.

作者信息

Li Sheng, Jiang Sheng, Jiang Wei, Zhou Yue, Shen Xiu-Yin, Luo Tao, Kong Ling-Ping, Wang Hua-Qiao

机构信息

Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.

Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China ; Department of Cardiothoracic Surgery, Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-sen University, Shantou, Guangdong 515000, P.R. China.

出版信息

Oncol Lett. 2015 Mar;9(3):1254-1260. doi: 10.3892/ol.2015.2869. Epub 2015 Jan 13.

Abstract

Crocetin is the main pharmacologically-active component of saffron and has been considered as a promising candidate for cancer chemoprevention. The purpose of the present study was to investigate the anticancer effects of crocetin and the possible mechanisms of these properties in the esophageal squamous cell carcinoma cell line KYSE-150. The KYSE-150 cells were cultured in Dulbecco's modified Eagle's medium and incubated with 0, 12.5, 25, 50, 100 or 200 μmol/l crocetin for 48 h. Cell proliferation was measured using an MTT assay. Hoechst 33258 staining and observation under fluorescent microscopy were used to analyze the proapoptotic effects of crocetin. The migration rate was assessed by a wound-healing assay. The cell cycle distribution was analyzed using flow cytometry analysis subsequent to propidium iodide staining. The expression of B-cell lymphoma-2-associated X protein (Bax) and cleaved caspase 3 was determined by western blot analysis. It was found that treatment of KYSE-150 cells with crocetin for 48 h significantly inhibited the proliferation of the cells in a concentration-dependent manner, and the inhibition of proliferation was associated with S phase arrest. Crocetin was also found to induce morphological changes and cell apoptosis in a dose-dependent manner through increased expression of proapoptotic Bax and activated caspase 3. In addition, crocetin suppressed the migration of KYSE-150 cells. The present study provides evidence that crocetin exerts a prominent chemopreventive effect against esophageal cancer through the inhibition of cell proliferation, migration and induction of apoptosis. These findings reveal that crocetin may be considered to be a promising future chemotherapeutic agent for esophageal cancer therapy.

摘要

西红花酸是藏红花的主要药理活性成分,被认为是癌症化学预防的一个有前景的候选物。本研究的目的是探讨西红花酸对食管鳞状细胞癌细胞系KYSE - 150的抗癌作用及其可能机制。将KYSE - 150细胞培养于杜氏改良 Eagle培养基中,分别用0、12.5、25、50、100或200 μmol/L的西红花酸处理48小时。采用MTT法检测细胞增殖。用Hoechst 33258染色并在荧光显微镜下观察,以分析西红花酸的促凋亡作用。通过伤口愈合试验评估迁移率。碘化丙啶染色后,采用流式细胞术分析细胞周期分布。通过蛋白质免疫印迹分析测定B细胞淋巴瘤-2相关X蛋白(Bax)和裂解的半胱天冬酶3的表达。结果发现,用西红花酸处理KYSE - 150细胞48小时可显著抑制细胞增殖,且呈浓度依赖性,增殖抑制与S期阻滞有关。还发现西红花酸通过增加促凋亡蛋白Bax的表达和激活半胱天冬酶3,以剂量依赖性方式诱导形态变化和细胞凋亡。此外,西红花酸抑制KYSE - 150细胞的迁移。本研究提供了证据表明,西红花酸通过抑制细胞增殖、迁移和诱导凋亡对食管癌发挥显著的化学预防作用。这些发现表明,西红花酸可能被认为是未来食管癌治疗中有前景的化疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac45/4315057/d0e94791f32c/OL-09-03-1254-g00.jpg

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