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雷公藤甲素在与U937细胞共接种时可抑制口腔癌细胞的增殖、侵袭、迁移和血管生成。

Triptolide represses oral cancer cell proliferation, invasion, migration, and angiogenesis in co-inoculation with U937 cells.

作者信息

Yang Cheng-Yu, Lin Chih-Kung, Lin Gu-Jiun, Hsieh Cheng-Chih, Huang Shing-Hwa, Ma Kuo-Hsing, Shieh Yi-Shing, Sytwu Huey-Kang, Chen Yuan-Wu

机构信息

Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.

Division of Anatomic Pathology, Taipei Tzu Chi Hospital, Taipei, Taiwan.

出版信息

Clin Oral Investig. 2017 Jan;21(1):419-427. doi: 10.1007/s00784-016-1808-1. Epub 2016 Apr 13.

Abstract

OBJECTIVES

Advanced oral cancer is a major public health concern because of a lack of effective prevention and treatment. Triptolide (TPL), a diterpenoid triepoxide derived from the Chinese herb Tripterygium wilfordii, has been demonstrated to possess strong anticancer properties. In this study, we investigated whether TPL exerts anticancer effects on the tumor microenvironment of head and neck squamous cell carcinoma (HNSCC).

MATERIALS AND METHODS

Human macrophage-like U937 cells were co-inoculated with oral cancer SAS cells in a noncontact transwell coculture system. Cytokine expression was detected using ELISA, and cell proliferation was detected using methylene blue. RNA levels were detected using qPCR. Protein levels were detected using Western blot analysis. In vivo experiments involved using xenografted NOD/SCID mice.

RESULTS

Our results demonstrated that TPL inhibited the growth of SAS cells co-inoculated with U937 cells in vitro and in vivo. TPL inhibited the invasion, migration ability, and angiogenesis of SAS cells co-inoculated with U937 cells. Expression of cytokines IL-6, IL-8, and TNF-α was induced by co-inoculation, but TPL repressed their expression.

CONCLUSION

TPL suppressed the expression of cytokines IL-6, IL-8, and TNF-α, as well as tumor growth, invasion, migration, and angiogenesis in the co-inoculation of human tongue cancer cells with macrophage-like U937 cells.

CLINICAL RELEVANCE

TPL is a potential candidate among novel chemotherapeutic agents or adjuvants for modulating tumor-associated macrophages in a tumor microenvironment of HNSCC.

摘要

目的

由于缺乏有效的预防和治疗方法,晚期口腔癌成为一个主要的公共卫生问题。雷公藤甲素(TPL)是一种从中药雷公藤中提取的二萜类三环氧物,已被证明具有强大的抗癌特性。在本研究中,我们调查了TPL是否对头颈部鳞状细胞癌(HNSCC)的肿瘤微环境具有抗癌作用。

材料与方法

在非接触式Transwell共培养系统中,将人巨噬细胞样U937细胞与口腔癌SAS细胞共同接种。使用ELISA检测细胞因子表达,使用亚甲蓝检测细胞增殖。使用qPCR检测RNA水平。使用蛋白质印迹分析检测蛋白质水平。体内实验涉及使用异种移植的NOD/SCID小鼠。

结果

我们的结果表明,TPL在体外和体内均抑制了与U937细胞共同接种的SAS细胞的生长。TPL抑制了与U937细胞共同接种的SAS细胞的侵袭、迁移能力和血管生成。共同接种诱导了细胞因子IL-6、IL-8和TNF-α的表达,但TPL抑制了它们的表达。

结论

在人舌癌细胞与巨噬细胞样U937细胞共同接种的情况下,TPL抑制了细胞因子IL-6、IL-8和TNF-α的表达,以及肿瘤生长、侵袭、迁移和血管生成。

临床意义

TPL是新型化疗药物或佐剂中调节HNSCC肿瘤微环境中肿瘤相关巨噬细胞的潜在候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c56a/5203829/565f3198bb64/784_2016_1808_Fig1_HTML.jpg

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