期刊
CHEMOTHERAPY
卷 67, 期 4, 页码 211-222出版社
KARGER
DOI: 10.1159/000518121
关键词
Colorectal cancer; Synergistic antitumor effects; Irinotecan; Endoplasmic reticulum stress; Immunogenic cell death
资金
- Science and Technology Program of Loudi [[2017]58]
The combination therapy of curcumin and irinotecan has synergistic antitumor effects by promoting immunogenic cell death. This may be an option for first-line chemotherapy in some patients with colorectal cancer.
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-gamma and TNF-alpha 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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