Quercetin inhibits malignant progression of high metastatic advanced colon cancer in hypoxia via suppressing ROS and PI3K/AKT pathway

作者：Pengfei Shang, Jiawei Yang, Lijun Shao, Chao Sun, Jian Ji, Xiaoyan Wang, Zongxue Zheng, Xiuli Guo · 发表于：Pharmaceutical Science Advances · 年份：2024 · DOI：10.1016/j.pscia.2024.100057 · 被引用次数：17 · 研究领域：Cancer, Hypoxia, and Metabolism、Sirtuins and Resveratrol in Medicine、Autophagy in Disease and Therapy

Advanced metastatic colon cancer is difficult to treat with existing chemotherapy medicines, and hypoxic microenvironment is closely related to angiogenesis and distant metastasis of colon cancer. Quercetin, a natural flavonoid, has been shown anti-tumor effects. The aim of this study is to investigate the effect of quercetin alone or combined with 5-FU on the invasion and metastasis of advanced metastatic or primary colorectal cancer in hypoxic environment. The cytotoxicity of quercetin or/and 5-FU on colon cancer cells using CCK8 assay, Hoechst 33342, flow cytometry and AO staining. The effects of quercetin or/and 5-FU on the migration and invasion were determined by transwell, cell scratching method and murine xenograft models. The potential mechanism was explored by Western blot and immunofluorescent assay. The results revealed quercetin effectively inhibited the invasion and migration of high metastatic advanced colon cancer LOVO cells under hypoxia through the inhibition of ROS and the expression of HIF-1α and PI3K/AKT pathway. Combination of quercetin and 5-FU could promote the inhibition of 5-FU on the invasion and migration of LOVO cells. Moreover, quercetin also significantly inhibited the proliferation of either LOVO cells or HT-29 cells under hypoxia by inducing apoptosis and autophagy, particularly, showing stronger inhibition on HT-29 cells than LOVO cells. In conclusion, quercetin inhibited the invasion and migration of advanced metastatic colon cancer LOVO cel...