2026 年第 1 期 第 21 卷

毛兰素重塑结直肠癌化疗应答的机制探索

Exploration of the mechanism by which erianin remodels chemotherapeutic response in colorectal cancer

作者：艾廉杰1孙志夫2芦维圆3

英文作者：Ai Lianjie1 Sun Zhifu2 Lu Weiyuan3

单位：1哈尔滨医科大学附属第四医院普外科，哈尔滨150001；2黑龙江中医药大学基础医学院，哈尔滨150040；3哈尔滨医科大学附属第六医院儿内科，哈尔滨150081

英文单位：1Department of General Surgery the Fourth Affiliated Hospital of Harbin Medical University Harbin 150001 China; 2School of Basic Medical Sciences Heilongjiang University of Chinese Medicine Harbin 150040 China; 3Department of Pediatric Medicine the Sixth Affiliated Hospital of Harbin Medical University Harbin 150081 China

关键词：结直肠癌；毛兰素；奥沙利铂；化疗应答；细胞凋亡；铁死亡

英文关键词：Colorectalcancer;Erianin;Oxaliplatin;Chemotherapeuticresponse;Cellapoptosis; Ferroptosis

• 摘要：

• 目的 探究毛兰素重塑结直肠癌化疗应答的机制。方法 以人结直肠癌细胞系HCT116和SW480为研究对象，将细胞分为空白对照组（仅加入正常培养基），奥沙利铂组（加入10 μmol/L奥沙利铂），毛兰素组（加入0、25、50 nmol/L毛兰素），联合组（加入10 μmol/L奥沙利铂及50 nmol/L毛兰素）。采用细胞计数试剂盒法检测细胞活力并计算半数抑制浓度（IC50）；克隆形成实验检测细胞增殖能力；流式细胞术评估细胞凋亡比例和细胞周期分布；利用相关试剂盒测定脂质过氧化水平、谷胱甘肽及丙二醛水平；蛋白免疫印迹法检测铁死亡相关蛋白［谷胱甘肽过氧化物酶4（GPX4）、溶质载体家族7成员11(SLC7A11)、长链脂酰辅酶A合成酶4(ACSL4)］表达。结果 对于HCT116和SW480细胞，毛兰素浓度升高和处理时间延长均会使细胞活力逐渐降低，且50 nmol/L毛兰素处理组细胞活力显著低于25 nmol/L处理组（P＜0.05），HCT116和SW480细胞的48 h IC50分别为30.2 nmol/L和101.4 nmol/L。单药处理组（奥沙利铂组、毛兰素组）的克隆形成率、谷胱甘肽含量、GPX4、SLC7A11蛋白水平均显著低于空白对照组，联合组的相关指标最低，较单药处理组进一步下降（均P＜0.05）。单药处理组的细胞凋亡率、脂质过氧化水平、丙二醛含量、ACSL4蛋白水平均显著高于空白对照组，联合组的相关指标最高，较单药处理组进一步升高（均P＜0.05）。与空白对照组相比，奥沙利铂组和毛兰素组均导致G2/M期阻滞，联合组的G2/M期细胞比例进一步升高，S期和G0/G1期细胞比例下降（均P＜0.05）。结论 毛兰素能抑制结直肠癌细胞活力，联合奥沙利铂可增强抑制效果，其机制可能与诱导细胞凋亡、阻滞细胞周期、促进铁死亡有关。

• Objective To explore the mechanism by which erianin remodels chemotherapeutic response in colorectal cancer. Methods Human colorectal cancer cell lines HCT116 and SW480 were used as research objects and divided into blank control group (only normal medium added), oxaliplatin group (10 μmol/L oxaliplatin added), erianin groups (0, 25, 50 nmol/L erianin added), and combination group (10 μmol/L oxaliplatin+50 nmol/L erianin added). Cell counting kit assay was used to detect cell viability and calculate half-maximal inhibitory concentration (IC50); colony formation assay was performed to evaluate cell proliferation ability; flow cytometry was used to assess cell apoptosis rate and cell cycle distribution; relevant kits were employed to determine lipid peroxidation level, glutathione and malondialdehyde levels; Western blot was used to detect the expression of ferroptosis-related proteins ［glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), long-chain acyl-CoA synthetase 4 (ACSL4)］. Results For HCT116 and SW480 cells, increased erianin concentration and prolonged treatment time both gradually reduced cell viability, and the cell viability in the 50 nmol/L erianin treatment group was significantly lower than that in the 25 nmol/L treatment group (P<0.05). The 48 h IC50 values of erianin for HCT116 and SW480 cells were 30.2 nmol/L and 101.4 nmol/L, respectively. The colony formation rate, glutathione content, and protein levels of GPX4 and SLC7A11 in the single-drug treatment groups (oxaliplatin group and erianin group) were significantly lower than those in the blank control group, and the relevant indicators in the combination group were the lowest, which were further decreased compared with the single-drug treatment groups (all P<0.05). The cell apoptosis rate, lipid peroxidation level, malondialdehyde content, and ACSL4 protein level in the single-drug treatment groups were significantly higher than those in the blank control group, and the relevant indicators in the combination group were the highest, which were further increased compared with the single-drug treatment groups (all P<0.05). Compared with the blank control group, both the oxaliplatin group and the erianin group induced G2/M phase arrest; the proportion of G2/M phase cells in the combination group was further increased, while the proportions of S phase and G0/G1 phase cells were decreased (all P<0.05). Conclusion  Erianin can inhibit the viability of colorectal cancer cells, and its combination with oxaliplatin can enhance the inhibitory effect. The mechanism may be related to inducing cell apoptosis, arresting cell cycle, and promoting ferroptosis.