Antitumor effects of IOX1 combined with bevacizumab-induced apoptosis and immunity on colorectal cancer cells

贝伐单抗 结直肠癌 细胞凋亡 免疫 医学 癌症研究 癌症 肿瘤科 免疫学 免疫系统 内科学 生物 化疗 遗传学
作者
Sheen‐Yie Fang,Huicun Cao,Hua Chen,Guangshao Cao,Tianxiao Li
出处
期刊:International Immunopharmacology [Elsevier]
卷期号:141: 112896-112896
标识
DOI:10.1016/j.intimp.2024.112896
摘要

Colorectal cancer (CRC), as a fatal cancer, is one of the most common cancers worldwide. Although the standard treatment for colorectal cancer is well researched and established, long-term patient survival remains poor, and mortality remains high. Therefore, more and more effective treatment options are needed. To evaluate the efficacy of bevacizumab, the histone demethylase inhibitor IOX1, or their combination for the treatment of colorectal cancer, we examined the effects of IOX1, bevacizumab, and IOX1 combined with bevacizumab on cell activity, proliferation, and migration of colorectal cancer cell lines HCT116, RKO, and CT26 by CCK8, colony formation assay, wound healing assay, and transwell assay. The effects of the drugs alone as well as in combination on apoptosis in colorectal cancer cell lines were examined by flow cytometry and further validated by Western blotting for apoptosis-related proteins. The antitumor effects of treatment alone or in combination on colorectal cancer cells were examined in animal models. Mice were injected subcutaneously with CT26 cells and the growth and immune infiltration in tumor tissues were detected by IHC after drug treatment. We found that IOX1 could effectively inhibit the activity of CRC cells and had a significant inhibitory effect on the proliferation and migration of CRC cells. The apoptosis rate increased in a dose-dependent manner after IOX1 treatment on colorectal cancer cells, and the expression of apoptosis-related proteins changed accordingly. Further combination with bevacizumab revealed that the combination had a more significant effect on the proliferation, migration, and apoptosis of CRC cells than either IOX1 or bevacizumab alone. In vivo experiments have found that both alone and combination drugs can inhibit the growth of mouse tumors, but the effect of combination inhibition is the most obvious. Combination therapy significantly inhibited the expression of proliferative marker (Ki67) in tumor xenograft models, and increased content of antigen-specific CD4
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