姜黄素抑制人神经母细胞瘤的初步实验探讨

Experimental study of inhibitory effects of curcumin in human neuroblastoma xenograft model

目的探讨姜黄素(CUR)抑制人神经母细胞瘤增殖作用。方法建立人神经母细胞瘤细胞株免疫活性C57BL/6j小鼠移植瘤模型,随机区组设计分配成四组:(1)生理盐水(NS)对照组,腹腔注射0.2 m L NS,作为阴性对照;(2)CUR组,按50 mg/kg,每2天给药1次,连续2周;(3)环磷酰胺(CP)组,按75 mg/kg给药,每周2次,连续2周,作为阳性对照;(4)CP+CUR组,CUR在CP给药前24 h给药,CUR与CP独立给药,时间和剂量同前。每组6只C57BL/6j小鼠,所有药物均于早晨9:00腹腔注射给药,每周监测相对肿瘤体积(RTV),治疗时间共2周,次日处死小鼠,称体质量、称瘤质量(Wt)、计算抑瘤率(IR),5-溴-2′-脱氧尿苷(Brd U)标记检测移植瘤细胞增殖。结果治疗2周后,CUR组RTV较NS组小,但大于CP组,CUR+CP组最低。随着治疗时间的延长,CUR组、NS组、CP组RTV均呈上升趋势,但CUR+CP组呈下降趋势。CUR组、CP组、CUR+CP组移植瘤的平均Wt分别为(4 342.0±445.6)、(1 369.0±327.4)、(301.2±73.1)mg,IR分别为46.82%、83.23%、96.31%,CUR组、CP组、CUR+CP组移植瘤平均Wt与NS组[(8 164.0±718.6)mg]比较,差异均有统计学意义(P<0.05),CP+CUR组移植瘤平均Wt与CP组比较,差异有统计学意义(P<0.05)。CUR组、CP组、CUR+CP组肿瘤增殖指数分别为0.135 7±0.023 0、0.119 2±0.016 4、0.039 1±0.013 8,与NS组(0.309 7±0.080 3)比较,差异有统计学意义(P<0.05),同时CP+CUR组与CUR组、CP组比较,差异均有统计学意义(P<0.05)。结论 CUR可抑制人神经母细胞移植瘤增殖,可能协同CP抗肿瘤生长。

Objective To study the antiproliferative effect of curcumin（CUR） on human neuroblastoma, and the syner- gistic effect of chemotherapy. Methods The 3-week-old immunocompetent C57BL/6j mice were transplanted with SK-N-SH ceils, distribution of randomized block design into 4 groups, 6 of each： （1）NS group tumor-bearing control group,0.2 mL of NS were intraperitoneally injected, as a negative control; （2）CUR group, according to 50 mg/kg injection, every other day, continuous two weeks; （3）cyclophosphamide （CP） group, according to 75 mg/kg injection, twice per week, total two weeks, as a positive control; （4）CP＋CUR group, CUR and CP independent administration, time and dose with the above, all drugs were administrated at 9：00a.m. Monitoring the relative tumor volume growth curves （RTV）weekly. The average weight （Wt） of the transplanted tumors and the tumor inhibitation rate （IR） were tested at two weeks after transplantation. Tumor cell proliferation was detected by bromouracil deoxyriboside labeling （BrdU）. Results At two weeks after transplantation, RTV of CUR groupwas smaller than that of the NS group, but bigger than that of the CP group, RTV of CUR＋CP group was the lowestoWith the increase of treatment time, RTV of CUR group, NS group, CP group were on the rise, but CUR＋CP group was on the decline.The average Wt in CUR group,CP group and CP＋CUR group were （4 342.0±445.6）, （1 369.0±327.4）, （301.2±73.1）mg respectively,the IR were 46.82%, 83.23% ,96.31% respectively ,compared with the average Wt in the NS group[（8 164.0±718.6）mg],the difference was statistical significance （P〈0.05）, the average Wt of the CP＋CUR group was significantly smaller than that of the CP group, the difference was statistical significance（P〈0.05 ）. The tumor proliferation index in the CUR group, CP group and CP＋CUR group were 0.135 7±0.023 0,0.119 2±0.016 4,0.039 1±0.013 8 respectively, compared with the NS group（0.309 7±0.080 3） ,the difference was statistical significance （P〈0.05）. The tumor proliferation index in CP＋CUR group was significantly smaller than that in the CP group or CUR group, the difference was statistical significance （P〈0.05）. Conclusion CUR can inhibit tumor proliferation and synergism CP anti-tumor growth in human neuroblastoma xenograft.