吉林大学学报（医学版）2025，Vol.51Issue(2)：428-436,9.DOI:10.13481/j.1671-587X.20250217
槲皮素对5-氟尿嘧啶诱导的人永生化角质形成细胞损伤的保护作用及其机制
Protective effect of quercetin against 5-fluorouracil-induced damage in human immortalized keratinocytes and its mechanism
摘要
Abstract
Objective:To investigate the protective effect of quercetin against 5-fluorouracil(5-FU)-induced damage in the human immortalized keratinocytes(HACAT),and to elucidate its possible mechanism.Methods:The HACAT cells were divided into control group(normal cultured cells),5-FU group(treated with 7.5 mg·L-1 5-FU for 24 h),and low,medium,and high doses of quercetin groups(HACAT cells treated with 25,50,and 75 μmol·L-1 quercetin combined with 7.5 mg·L-15-FU for 24 h).Cell counting kit-8(CCK-8)assay was used to detect the survival rates of HACAT cells treated with different doses(0,10,25,50,75 and 100 μmol·L-1)of quercetin in various groups.The fluorescent probe of reactive oxygen species(ROS)was used to detect ROS levels in the HACAT cells in various groups.Annexin Ⅴ-FITC/PI double staining was used to detect the apoptosis of HACAT cells in various groups.Western blotting method was used to detect the expression levels of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),Cleaved Caspase-3,cyclooxygenase-2(COX-2),interleukin-1 β(IL-1β),and interleukin-6(IL-6)in the HACAT cells in various groups.Results:The CCK-8 assay results showed that compared with 0 μmol·L-1 quercetin group,the survival rates of HACAT cells in 10,25,50 and 75 μmol·L-1quercetin groups showed no significant differences(P＞0.05),while the survival rates of HACAT cells in 100 μmol·L-1 quercetin group was significantly decreased(P＜0.05).Compared with 5-FU group,the survival rates of the HACAT cells in low,medium and high doses of quercetin group were significantly increased(P＜0.05).Compared with 5-FU group,the ROS levels in low,medium,and high doses of quercetin groups were significantly decreased(P＜0.05).Annexin Ⅴ-FITC/PI double staining assay showed that compared with 5-FU group,the apoptotic rates in low,medium and high doses of quercetin groups were significantly decreased(P＜0.05).The Western blotting results showed that compared with 5-FU group,the expression levels of Bcl-2 protein in medium and high doses of quercetin groups were significantly increased(P＜0.05),the expression levels of Bax and Cleaved Caspase-3 proteins in low,medium and high doses of quercetin groups were significantly decreased(P＜0.05),the expression levels of COX-2 protein in medium and high doses of quercetin groups were significantly decreased(P＜0.05),and the expression levels of IL-1β and IL-6 proteins in medium dose of quercetin group were significantly decreasd(P＜0.05).Conclusion:Quercetin has protective effect on 5-FU-induced damage in the HACAT cells,and its mechanism may be related to the reduction of the expression of ROS and inflammatory factor COX-2 which attenuate the apoptosis.关键词
槲皮素/手足综合征/人永生化角质形成细胞/细胞凋亡/环氧合酶2Key words
Quercetin/Hand-foot syndrome/Human immortalized keratinocytes/Apoptosis/Cyclooxygenase-2分类
中医学引用本文复制引用
李佳欣,王一,吴婷婷,郝诗睿,付晓..槲皮素对5-氟尿嘧啶诱导的人永生化角质形成细胞损伤的保护作用及其机制[J].吉林大学学报（医学版）,2025,51(2):428-436,9.基金项目
国家中医药管理局第五批全国中医临床优秀人才研修项目(国中医药人教函[2022]1号) （国中医药人教函[2022]1号）
辽宁省卫健委第一批优秀中医临床人才培养项目(辽中医药函[2021]1号) （辽中医药函[2021]1号）
辽宁省科技厅自然科学基金项目(2019-ZD-0809) （2019-ZD-0809）
