| 摘要: |
| 目的 通过体内和体外实验，探讨金雀异黄素（Gen）与5-氟尿嘧啶（5-FU）联用对肝癌的化疗增敏效果。方法 体外实验中根据干预方法分别将人肝癌细胞株Bel-7404、SMMC-7721和HepG2分为溶剂对照（NC）组、10 μmol/L Gen处理组、2 μmol/L 5-FU处理组及Gen+5-FU联合处理组，利用CCK-8法及流式细胞技术研究Gen与5-FU联用对肝癌细胞增殖和凋亡的影响。体内实验分别构建Bel-7404肿瘤细胞系异种移植（CDX）和Liver-0117人源肿瘤组织异种移植（PDX）裸小鼠模型，然后将荷瘤裸小鼠模型分为4组：NC组、Gen处理组、5-FU处理组和Gen+5-FU联合处理组，观察不同剂量Gen与5-FU单独或联合处理肝癌模型对肿瘤生长的影响。结果 在处理24、48、72 h后，Gen+5-FU联合处理组Bel-7404、SMMC-7721和HepG2细胞增殖率均低于NC组、Gen处理组及5-FU处理组（P均< 0.01）；处理72 h后Gen+5-FU联合处理组Bel-7404、SMMC-7721和HepG2细胞凋亡率均高于NC组、Gen处理组及5-FU处理组（P均< 0.01）。对于Bel-7404荷瘤裸小鼠，给药28 d后NC组、Gen（15 mg/kg）处理组、5-FU（30 mg/kg）处理组、Gen（15 mg/kg）+5-FU（20 mg/kg）联合处理组肿瘤相对体积（RTV）分别为15.35±2.92、17.51±3.11、12.93±4.88、13.67±3.54，组间差异无统计学意义（F=1.822，P>0.05）；提高Gen剂量至40 mg/kg干预21 d后，Gen（40 mg/kg）处理组的RTV低于NC组（9.73±5.85 vs 17.54±5.06），差异有统计学意义（P < 0.05）。对于PDX模型Liver-0117荷瘤裸小鼠，给药18 d后，Gen（15 mg/kg）+5-FU（20 mg/kg）联合处理组的RTV低于5-FU（30 mg/kg）处理组（12.64±0.92 vs 18.76±0.68），差异有统计学意义（P < 0.05），相对肿瘤抑制率（T/C）为0.576。结论 Gen与5-FU联用在体外表现出较好的化疗增敏效果，但对于不同荷瘤裸小鼠模型其增敏效果不同。 |
| 关键词: 金雀异黄素 5-氟尿嘧啶 化疗增敏作用 肝细胞癌 |
| DOI：10.16781/j.0258-879x.2021.12.1355 |
| 投稿时间：2020-09-29 |
| 基金项目: |
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| Chemosensitization effects of genistein combined with 5-fluorouracil on hepatocellular carcinoma |
| GUO Yu-ling1,YAN Pei-song2,SONG Li-hua1* |
(1. Department of Food Science & Technology, Shanghai Jiao Tong University School of Agriculture and Biology, Shanghai 200240, China;
2. School of Basic Medicine, Fudan University, Shanghai 200433, China
*Corresponding author) |
| Abstract: |
| Objective To investigate the chemosensitization effects of genistein (Gen) combined with 5-fluorouracil (5-FU) on hepatocellular carcinoma in vitro and in vivo.Methods In the in vitro experiments, human hepatocellular carcinoma cell lines (Bel-7404, SMMC-7721 and HepG2) were used in negative control (NC) group, Gen group (10 μmol/L), 5-FU group (2 μmol/L) as well as Gen+5-FU group according to the intervention methods. The effects of Gen combined with 5-FU on the proliferation and apoptosis of hepatocellular carcinoma cells were analyzed by cell counting kit 8 (CCK-8) method and flow cytometry. Bel-7404 cell line-derived xenograft (CDX) and Liver-0117 patient-derived xenograft (PDX) mouse models were constructed in vivo. Then the tumor-bearing mouse models were divided into 4 groups:NC group, Gen group, 5-FU group and Gen+5-FU group. The effects of different treatment methods on tumor growth were observed.Results The proliferation rates of Bel-7404, SMMC-7721 and HepG2 cells in the Gen+5-FU group were significantly lower than those in the Gen group and 5-FU group (all P < 0.01) after 24, 48 and 72 h of treatment; the average apoptosis rates of these cells were significantly higher in the Gen+5-FU group than in the NC group, Gen group and 5-FU group after 72 h of culture (all P < 0.01). The relative tumor volumes (RTVs) of the Bel-7404 CDX tumor-bearing mice in the NC group, Gen (15 mg/kg) group, 5-FU (30 mg/kg) group and Gen (15 mg/kg)+5-FU (20 mg/kg) group 28 d after administration were 15.35±2.92, 17.51±3.11, 12.93±4.88 and 13.67±3.54, respectively, showing no significant difference (F=1.822, P > 0.05); after increasing the dose of Gen to 40 mg/kg for 21 d, the RTV of the Gen (40 mg/kg) group was significantly lower than that of the NC group (9.73±5.85 vs 17.54±5.06, P < 0.05). The RTV of the Liver-0117 PDX tumor-bearing mice in the Gen (15 mg/kg)+5-FU (20 mg/kg) group 18 d after administration was significantly lower than that in the 5-FU (30 mg/kg) group (12.64±0.92 vs 18.76±0.68, P < 0.05), and the ratio of RTV between treatment group and control group was 0.576.Conclusion Gen combined with 5-FU shows good chemosensitization effects in vitro, which are varied on different models of tumor-bearing mice. |
| Key words: genistein 5-fluorouracil chemosensitization hepatocellular carcinoma |
