目的：探讨quercetin 对肝癌细胞体内生长的抑制作用及机制。方法：用人肝癌HepG2 细胞皮下接种法建立裸鼠移植瘤模型，成瘤后随机分为对照组、quercetin 治疗组、5-FU 治疗组、5-FU+quercetin 联合治疗组，溶剂或药物均1 次/d 腹腔注射，3 周后观察各组移植瘤大小并计算各治疗组的抑瘤率，分别用RT-PCR、Western blot、免疫组化法检测各组移植瘤组织中cyclin D1、cyclin E、增殖细胞核抗原（PCNA）的表达。结果：与对照组比较，各治疗组移植瘤体积明显减小、移植瘤组织中cyclin D1、cyclin E mRNA 和蛋白表达以及PCNA 阳性指数均明显降低（均P<0.05），其中联合治疗组的抑瘤率明显大于两个单药组，cyclin D1、cyclin E、PCNA 表达的降低程度也明显大于两个单药组（均P<0.05），而两个单药组间各项指标差异均无统计学意义（均P>0.05）。结论：quercetin 能通过下调cyclin D1 与cyclin E 的表达而抑制肝癌细胞的增殖，且与5-FU 联合应用具有协同作用。
Quercetin inhibiting growth of hepatocellular carcinoma cells: in vivo experimental study
Objective: To investigate the inhibitory effect of quercetin on the growth of hepatocellular carcinoma (HCC) cells in vivo and the mechanism. Methods: Tumor xenograft model was established by subcutaneous inoculation of human HCC HepG2 cells into the nude mice. After tumor formation, the tumor-bearing mice were randomly divided into control group, quercetin treatment group, 5-FU treatment group, and quercetin plus 5-FU combination treatment group, and the vehicle or drugs were administered by intraperitoneal injection once daily. At three weeks after treatment, the tumor size in each group was observed and the tumor inhibition rate in each treatment group was calculated, and the expressions of cyclin D1, cyclin E and proliferating cell nuclear antigen (PCNA) in the xenograft tumor tissues were determined by RT-PCR, Western blot and immunohistochemical staining, respectively. Results: Compared with control group, the tumor size was reduced, and the mRNA and protein expressions of cyclin D1 and cyclin E as well as PCNA positive index in tumor tissue were decreased significantly in each treatment group (all P<0.05), where the tumor inhibition rate in combination treatment group was significantly greater, and the decreasing degrees in expressions of cyclin D1, cyclin E and PCNA were all significantly larger than that in either of the single agent treatment group (all P<0.05), but all the parameters between the two single agent treatment groups showed no significant difference (all P>0.05). Conclusion: Quercetin can inhibit the proliferation of HCC cells by down-regulating cyclin D1 and cyclin E expressions, and may exert a synergistic action in combination with 5-FU.