Curcumin Suppresses the Progression of Colorectal Cancer by Improving Immunogenic Cell Death Caused by Irinotecan.

IF 2 4区医学 Q3 ONCOLOGY

Chemotherapy Pub Date : 2022-01-01 Epub Date: 2022-07-27 DOI:10.1159/000518121

Cunliang Zhu, Zhaobi Fang, Lei Peng, Fan Gao, Wei Peng, Fengqian Song

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引用次数: 8

Abstract

Background: Irinotecan (IRI) is a common chemotherapeutic drug for colorectal cancer; however, the mechanism underlying its immunomodulatory effect remains unclear. Curcumin (CUR), an adjuvant drug with anti-inflammatory and antitumor effects, has been studied extensively, although its synergistic antitumor effect remains unclear.

Methods: The effects of CUR and IRI on oxidative stress and their antitumor effects were detected by flow cytometry. Endoplasmic reticulum stress-related proteins including CHOP and BiP, and immunogenic cell death (ICD) proteins including calreticulin (CALR) and high mobility group box 1 (HMGB1), were detected by Western blotting. IFN-γ and TNF-α levels in the serum of mice were detected by ELISA.

Results: IRI in combination with CUR had synergistic antitumor effects in CT-26 colon carcinoma cells. Combination treatment with IRI and CUR was more effective than IRI or CUR alone. IRI and CUR combination treatment significantly upregulated ICD-related proteins including CALR and HMGB1 and had a greater antitumor effect than IRI or CUR single treatment in vivo. CUR may synergistically improve the antitumor effect of IRI by promoting the ICD effect.

Conclusion: Combination therapy with IRI and CUR may be an option for first-line chemotherapy in some patients with advanced colorectal cancer.

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姜黄素通过改善伊立替康引起的免疫原性细胞死亡来抑制结直肠癌的进展。

背景:伊立替康(Irinotecan, IRI)是结直肠癌常用的化疗药物;然而，其免疫调节作用的机制尚不清楚。姜黄素(Curcumin, CUR)是一种具有抗炎和抗肿瘤作用的辅助药物，已被广泛研究，但其协同抗肿瘤作用尚不清楚。方法:采用流式细胞术检测CUR和IRI对氧化应激的影响及其抗肿瘤作用。Western blotting检测内质网应激相关蛋白CHOP和BiP，免疫原性细胞死亡蛋白calreticulin (CALR)和高迁移率组盒1 (HMGB1)。ELISA法检测小鼠血清中IFN-γ、TNF-α水平。结果:IRI联合CUR对CT-26结肠癌细胞具有协同抗肿瘤作用。IRI和CUR联合治疗比IRI或CUR单独治疗更有效。IRI和CUR联合治疗显著上调CALR和HMGB1等icd相关蛋白，体内抗肿瘤效果优于IRI或CUR单独治疗。CUR可能通过促进ICD作用协同提高IRI的抗肿瘤作用。结论:IRI和CUR联合治疗可能是一些晚期结直肠癌患者一线化疗的一种选择。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Chemotherapy 医学-药学

CiteScore

5.80

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： This journal publishes original research articles and state-of-the-art reviews on all aspects of antimicrobial and antitumor chemotherapy. The results of experimental and clinical investigations into the microbiological and pharmacologic properties of antibacterial, antiviral and antitumor compounds are major topics of publication. Papers selected for the journal offer data concerning the efficacy, toxicology, and interactions of new drugs in single or combined applications. Studies designed to determine the pharmacokinetic and pharmacodynamics properties of similar preparations and comparing their efficacy are also included. Special emphasis is given to the development of drug-resistance, an increasing problem worldwide.