四君子汤诱导裸小鼠移植性人胃癌细胞凋亡的初步研究

目的:研究健脾类中药四君子汤在体内诱导移植性人胃癌细胞凋亡的作用。方法:采用人胃癌细胞SGC7901裸小鼠皮下移植瘤模型。实验动物共30只,造模后随机分为3组,每组10只。四君子汤组,予四君子汤煎剂灌胃;5FU组,5FU腹腔注射,共6天;对照组,予生理盐水灌胃,共40天。应用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法(TUNEL法)、电镜观察结合流式细胞分析技术,观察四君子汤的抑瘤作用及细胞形态学改变,并计算肿瘤细胞凋亡率。结果:发现四君子汤对裸小鼠移植性人胃癌细胞瘤抑瘤率为34.33%,TUNEL法检测肿瘤细胞凋亡指数AI为16.24%±3.21%,与对照组的2.63%±1.03%比较明显提高t检验P<0.01;流式细胞分析示四君子汤组凋亡率为11.38%±6.46%,比对照组的7.15%±1.32%提高(t检验P<0.05);电镜下见凋亡细胞染色质浓聚成块,位于核周边,胞浆浓缩。结论:四君子汤有诱导裸小鼠移植性人胃癌细胞凋亡的作用,其对胃癌治疗的价值有必要进一步研究。

Apoptosis Induction by Sijunzi Decoction in Human Gastric Cancer Xenografts in Nude Mice

Objective: The current study was designed to examine whether Sijunzi decoction could induce apoptosis in human gastric cancer xenografts in nude mice. Methods: A human gastric adenocarcinoma cell line SGC-7901 was grafted into 30 nude mice. The animals in two experimental groups received either Sijunzi decoction for 40 days or 5-fluorouracil (5-FU) for 6 days beginning 2 days after grafting. The control animals received saline according to an identical schedule. The animals were sacrified 41 days after grafting. The therapeutic effect was determined by measuring of tumor size and tumor weight. Apoptotic indices were examined with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate fluorescence nick end labeling (TUNEL) method and flow cytometry analysis. Morphological changes were observed by electron microscopy. Results: Comparing with controls, tumor growth was significantly inhibited by Sijunzi decoction ( 34.33％ ， P<0.05) or 5 FU( 50.00％ ， P< 0.05) . Apoptotic index(AI) was significantly higher(16.24％ ± 3.21％ as determined by TUNEL and 11.38％ ± 6.46％ by FACScan) in Sijunzi decoction treatment group than that in the control group (TUNEL:2.63％ ± 1.03％ ,P< 0.01; FACScan:7.15％ ± 1.32％ ,P< 0.05); while there was no significant increase of AI in 5 FU treatment group. Cell shrinkage, nuclear chromatin condensation, formation of membrane blebs and apoptotic bodies were frequently observed on tumor sections in Sijunzi decoction group, while only few apoptotic cells/bodies and necrotic cells were found in the 5-FU treatment group, and in control group cancer cells were in proliferation. Conclusions: The data demonstrated enhanced apoptosis in human gastric cancer xenografts in nude mice after treatment with Sijunzi decoction, suggesting that Sijunzi decoction may be a potential anticancer agent for gastric cancer treatment.