Curcumol increases the sensitivity of colon cancer to 5-FU by regulating Wnt/β-catenin signaling

作者：Jinfeng Gao, Daorong Hou, Ping Hu, Guoxin Mao · 发表于：Translational Cancer Research · 年份：2021 · DOI：10.21037/tcr-21-689 · 被引用次数：28 · 研究领域：Curcumin's Biomedical Applications、Wnt/β-catenin signaling in development and cancer、Pharmacological Effects of Medicinal Plants

BACKGROUND: 5-fluorouracil (5-FU) resistance is the leading cause of treatment failure in colon cancer. Combination therapy is an effective strategy to inhibit cancer cells and prevent drug resistance. Therefore, we studied the antitumor effect of curcumol alone or combined with 5-FU on human colon cancer drug-resistant cells. METHODS: The 5-FU resistant HCT116 cell line (HCT116/5-FU) was established by repeated exposure to gradually increasing concentrations of 5-FU; Cell viability was measured by cell counting kit-8 (CCK-8); apoptosis rate of HCT116 cells was detected using Annexin V-fluorescein isothiocyanate (FITC) assay kit; cell proliferation and invasion were detected using colony formation assays, wound healing assay and transwell invasion assays; activity of transplanted tumor in vivo in specific pathogen free (SPF) BALB/c nude mice (6 weeks old, male) was monitored by bioluminescence imaging, immunohistochemistry and western blot analysis. RESULTS: Our study showed the potent antitumor effect of curcumol by induction of apoptosis, inhibition of proliferation, invasion, migration, and improvement of the therapeutic efficacy of 5-FU toward human colon cancer HCT116 cells. From our results, curcumol could chemosensitize 5-FU-resistant HCT116 cells. The combination of curcumol and 5-FU exerted a synergistic inhibitory effect on the induction of apoptosis. Also, this combination inhibited the proliferation, invasion, and migration of both chemo-resistant and sensitive ce...