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6-姜烯酚通过增加缺氧/低糖条件下结肠癌细胞的凋亡和自噬增强氟尿嘧啶、奥沙利铂和伊立替康的抗癌作用。

6-Shogaol enhances the anticancer effect of 5-fluorouracil, oxaliplatin, and irinotecan via increase of apoptosis and autophagy in colon cancer cells in hypoxic/aglycemic conditions.

机构信息

Department of Pathology, Wroclaw Medical University, ul. K. Marcinkowskiego, 150-368, Wrocław, Poland.

Department of Chemistry, Wroclaw University of Science and Technology, Wrocław, Poland.

出版信息

BMC Complement Med Ther. 2020 May 11;20(1):141. doi: 10.1186/s12906-020-02913-8.

DOI:10.1186/s12906-020-02913-8
PMID:32393373
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7216385/
Abstract

BACKGROUND

The development and growth of colorectal cancer based on constitutive activation of numerous signaling pathways that stimulate proliferation and metastasis. Plant-derived agents excel by targeting multiple aspects of tumor progression. Previous investigations have shown that ginger derivatives- shogaols possess anti-cancer and anti-inflammatory effects. In the present study, we have examined the anti-cancer effects of 6-shogaol alongside with the most widely used chemotherapeutic agents/regimens in the tumor-like microenvironment conditions.

METHODS

Cytotoxicity on two colon cancer cell lines (SW480 and SW620) was measured by MTT test. Apoptosisassay, immunocytochemical and Western blotting analysis for autophagy and apoptosis detection were performed.

RESULTS

Here, we report that 6-shogaol by itself or in combination with chemotherapeutic agents/regimens exerted a cytotoxic effect on CRC cells. Cell death might be linked with the activation of autophagy and apoptosis-related pathways. In the tumor-like microenvironment, which is characterized by hypoxia and glucose starvation, 6-shogaol with chemotherapeutics is significantly more potent than conventional chemotherapy alone.

CONCLUSIONS

Collectively, our data suggest that the addition of 6-shogaol to established chemotherapeutic regimens could potentially be a remarkable therapeutic strategy for colorectal cancer.

摘要

背景

结直肠癌的发生和发展基于众多信号通路的组成性激活,这些信号通路刺激增殖和转移。植物衍生剂通过针对肿瘤进展的多个方面而表现出色。先前的研究表明,姜衍生的-姜烯酚具有抗癌和抗炎作用。在本研究中,我们在类似于肿瘤微环境的条件下,检查了 6-姜烯酚与最广泛使用的化疗药物/方案的抗癌作用。

方法

通过 MTT 试验测量两种结肠癌细胞系(SW480 和 SW620)的细胞毒性。进行凋亡检测、免疫细胞化学和 Western blot 分析以检测自噬和凋亡。

结果

在这里,我们报告 6-姜烯酚本身或与化疗药物/方案联合使用对 CRC 细胞具有细胞毒性作用。细胞死亡可能与自噬和凋亡相关途径的激活有关。在以缺氧和葡萄糖饥饿为特征的类似肿瘤的微环境中,6-姜烯酚与化疗药物的联合使用比单独使用常规化疗更有效。

结论

总的来说,我们的数据表明,将 6-姜烯酚添加到既定的化疗方案中可能是治疗结直肠癌的一种有前途的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cf7/7216385/d40460634149/12906_2020_2913_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cf7/7216385/d28431bbf062/12906_2020_2913_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cf7/7216385/373aeb0091fa/12906_2020_2913_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cf7/7216385/5fe2fffee06a/12906_2020_2913_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cf7/7216385/1a7fa21ef324/12906_2020_2913_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cf7/7216385/d40460634149/12906_2020_2913_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cf7/7216385/d28431bbf062/12906_2020_2913_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cf7/7216385/373aeb0091fa/12906_2020_2913_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cf7/7216385/5fe2fffee06a/12906_2020_2913_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cf7/7216385/1a7fa21ef324/12906_2020_2913_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cf7/7216385/d40460634149/12906_2020_2913_Fig5_HTML.jpg

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