摘要
目的:研究白花蛇舌草总黄酮(FHD)对人肝癌细胞SMMC-7721,BEL-7402的体外抑制作用,对小鼠移植性肝癌H22的体内抑制作用和对其增殖周期、凋亡、免疫功能的影响.方法:MTT法评价FHD在0,5,10,50,100 mg/L浓度下,于24,48,72h对人肝癌细胞SMMC-7721,BEL-7402的抑制率变化.昆明♂小鼠60只,随机取10只为正常对照组,余接种H22瘤株,随机分为模型对照组、5-FU阳性对照组(30 mg/kg)和高中低剂量FHD给药组(剂量分别为25,50,100 mg/kg),腹腔给药10d后,比较各组瘤质量抑制率、H22细胞周期分布及凋亡率,比较各组荷瘤小鼠的胸腺指数(×10^(-3))、脾脏指数(×10^(-3))、脾淋巴细胞转化率和血清TNF-α、IFN-γ水平(ng/L).结果:FHD对SMMC-7721、BEL-7402细胞具有体外抑制作用,且呈剂量依赖性和时间依赖性(P<0.05).与模型对照组相比,25,50,100 mg/kg FHD显著抑制小鼠移植性H22肿瘤(P<0.01),使G_0/G_1期H22细胞比例逐渐增加(30.36%±5.72%,32.83%±6.67%,39.67%±8.01% vs 25.62%±4.36%,P<0.05或P<0.01),G_2/M期细胞比例逐渐下降(7.65%±2.32%,6.33%±3.43%,2.22%±0.98% vs 11.13%±2.77%,P<0.05或P<0.01),促进肿瘤细胞凋亡(2.41%±0.42%,2.22%±0.33%,2.07%±0.40% vs 1.47%±0.66%,P<0.01),降低荷瘤小鼠脾脏指数(51.43±8.31,47.43±7.89,48.64±9.35 vs 67.63±7.44,P<0.01),升高胸腺指数(33.36±4.09,40.35±5.79,34.57±6.56 vs 22.43±4.52,P<0.01)和脾淋巴细胞转化率(10.83%±3.75%,11.33%±5.04%,13.58%±4.62% vs 9.35%±2.02%,P<0.05),并提高血清TNF-α(257.56±42.29,386.36±25.97,364.52±23.62 vs 101.43±24.72,P<0.01)、IFN-γ水平(355.83±35.74,392.31±25.17,357.38±34.82 vs 172.35±29.02,P<0.01).结论:FHD在体外、体内均具有抑制肝癌细胞的作用,此作用与阻滞肿瘤细胞增殖周期、促进肿瘤细胞凋亡、调节机体免疫环境有关.
AIM： To investigate the inhibitory effect of favonoids from Hedyotis diffusa willd. （FHD） on human hepatoma cell line SMMC-7721 and BEL-7402 in vitro, the antitumor effect on transplanted H22 tumor cells in vivo and its influence on the proliferation cycle, apoptosis of tumor cells and immune circumstances.
METHODS： MTT assay was used to measure the inhibition of SMMC-7721 and BEL-7402 cells exposing to 0, 5, 10, 50 and 100 mg/L FHD for 24, 48 and 72 hours. Sixty Kunming mice were randomly and averagely divided into 6 groups. Except those in normal control group, the other mice received inoculation of H22 tumor cells, and then treated with normal saline, 5-fluorouracil （30 mg/kg）, and FHD （25, 50, 100 mg/kg）, respectively, for 10 days. The following indicators were compared among the 6 groups, including the inhibitory rates of tumor weights, the distribution of H22 cell cycle, the apoptosis of H22 cells, the thymus index （× 10^-3） and splenic index （× 10^-3） in mice bearing H22 tumors, the splenic lymphocyte transformation efficiency, and the serum levels （ng/L） of tumor necrosis factor （TNF-α） and interferon-γ （IFN-γ）.
RESULTS： FHD inhibited the proliferation of SMMC-7721 and BEL-7402 cells in vitro in a dose- and time-dependent manner. In compari- son with those in the model control mice, when FHD was used at the concentrations of 25, 50 and 100 mg/kg, the growth of H22 tumors was obviously restrained （P 〈 0.01）; the proportion of G0/Gl·phase cells was increased （30.36% ± 5.72%, 32.83% ±6.67%, 39.67% ± 8.01% vs 25.62% ±4.36%, P 〈 0.05 or P 〈 0.01）, while that of G2/ M-phase cells was decreased （7.65% ± 2.32%, 6.33% ±3.43%, 2.22% ± 0.98% vs 11.13% ± 2.77%, P 〈 0.05 or P 〈 0.01）; the apoptosis of tumor cells was significantly promoted （2.41% ±0.42%, 2.22% ±0.33%, 2.07% ±0.40% vs 1.47% ±0.66%, P 〈 0.01）; the splenic index was down-regulated （51.43 ±8.31, 47.43 ±7.89, 48.64 ± 9.35 vs 67.63 ±7.44, P 〈 0.01）, but the thymus index （33.36 ±4.09, 40.35 ±5.79, 34.57 ±6.56 vs 22.43 ±4.52, P 〈 0.01）, the splenic lymphocyte transformation rate （10.83% ± 3.75%, 11.33% ± 5.04%, 13.58% ± 4.62% vs 9.35% ± 2.02%, P 〈 0.05）, and the serum levels of TNF-α （257.56 ± 42.29, 386.36 ± 25.97, 364.52 ± 23.62 vs 101.43 ± 24.72, P 〈 0.01） and IFN-γ （355.83 ± 35.74, 392.31 ± 25.17, 357.38 ± 34.82 vs 172.35 ± 29.02, P 〈 0.01） were markedly elevated.
CONCLUSION： FHD has inhibitory effect on hepatoma cells both in vivo and in vitro, which is related to the blocking of tumor cell proliferation cycle, promotion of tumor cell apoptosis and regulation of immune circumstances.
出处
《世界华人消化杂志》
CAS
北大核心
2007年第12期1347-1352,共6页
World Chinese Journal of Digestology
关键词
白花蛇舌草
总黄酮
肝癌
抑制作用
增殖周期
凋亡
免疫
肿瘤坏死因子-α
干扰素-γ
MTT法
Hedyotis diffusa wilid.
Flavonoids
Hepatoma
Inhibitory effect
Cell proliferation cycle
Apoptosis
Immunization
Tumor necrosis factor-α
Interferon-γ
