中华肝脏病杂志
中華肝髒病雜誌
중화간장병잡지
Chinese Journal of Hepatology
2015年
9期
669-674
,共6页
胡高裕%黄赞松%周喜汉%胡静%黄炳臣
鬍高裕%黃讚鬆%週喜漢%鬍靜%黃炳臣
호고유%황찬송%주희한%호정%황병신
癌,肝细胞%苦参碱%顺铂%存活素%半胱氨酸-天冬氨酸蛋白酶-3
癌,肝細胞%苦參堿%順鉑%存活素%半胱氨痠-天鼕氨痠蛋白酶-3
암,간세포%고삼감%순박%존활소%반광안산-천동안산단백매-3
Carcinoma,hepatocellular%Matrine%Cisplatin%Survivin%Caspase-3
目的 观察苦参碱(Ma)联用顺铂(DDP)对人肝癌裸鼠移植瘤生长的影响并探讨其作用的可能分子机制. 方法 将人肝癌细胞株HepG2注入BALB/c裸鼠腋部皮下建立移植瘤模型,待成瘤后,随机分为4组:对照组、Ma组、DDP组及Ma和DDP联合组,均采用腹腔注射给药.期间观察记录裸鼠的体质量和肿瘤体积,绘制体质量变化曲线与瘤体生长曲线图;用药14d后处死实验裸鼠称瘤重,计算抑瘤率;免疫组织化学法检测瘤组织中凋亡相关蛋白存活素与半胱氨酸-天冬氨酸蛋白酶-3 (caspase-3)的表达.多组间数据比较采用单因素方差(ANOVA)分析,两组间比较采用两独立样本t检验. 结果 Ma或DDP单用对裸鼠移植瘤抑瘤率分别为37.5％和75.0％,Ma和DDP联用可明显抑制瘤体生长(P＜0.05),其抑瘤率达83.3％,明显高于Ma或DDP单用组.Ma+DDP组裸鼠的平均体质量为21.50 g,比对照组(28.50 g)及Ma组(26.67 g)低,但较DDP组(17.33 g)高,且精神、活动、食量等全身状况也明显优于DDP组,瘤组织中细胞存活素阳性率为19.58％±4.52％,较对照组(83.26％±15.56％)、Ma组(62.50％±8.09％)及DDP组(38.67％±8.26％)降低(P＜0.05).与之相对,NS组、Ma组及DDP组caspase-3的阳性细胞率分别为21.15％±3.68％、35.13％±10.57％、65.88％±4.81％,而Ma+DDP组较之明显升高,为78.26％±6.09％,Ma+DDP组与其他组比较,差异均具有统计学意义(P＜0.05). 结论 Ma或DDP单用对裸鼠移植瘤具有抑制作用,Ma与DDP联用能增强DDP对裸鼠移植瘤的抑瘤作用和改善全身状况,降低DDP的不良反应.其可能的作用机制是影响存活素和caspase-3的表达,诱导肿瘤细胞凋亡.
目的 觀察苦參堿(Ma)聯用順鉑(DDP)對人肝癌裸鼠移植瘤生長的影響併探討其作用的可能分子機製. 方法 將人肝癌細胞株HepG2註入BALB/c裸鼠腋部皮下建立移植瘤模型,待成瘤後,隨機分為4組:對照組、Ma組、DDP組及Ma和DDP聯閤組,均採用腹腔註射給藥.期間觀察記錄裸鼠的體質量和腫瘤體積,繪製體質量變化麯線與瘤體生長麯線圖;用藥14d後處死實驗裸鼠稱瘤重,計算抑瘤率;免疫組織化學法檢測瘤組織中凋亡相關蛋白存活素與半胱氨痠-天鼕氨痠蛋白酶-3 (caspase-3)的錶達.多組間數據比較採用單因素方差(ANOVA)分析,兩組間比較採用兩獨立樣本t檢驗. 結果 Ma或DDP單用對裸鼠移植瘤抑瘤率分彆為37.5％和75.0％,Ma和DDP聯用可明顯抑製瘤體生長(P＜0.05),其抑瘤率達83.3％,明顯高于Ma或DDP單用組.Ma+DDP組裸鼠的平均體質量為21.50 g,比對照組(28.50 g)及Ma組(26.67 g)低,但較DDP組(17.33 g)高,且精神、活動、食量等全身狀況也明顯優于DDP組,瘤組織中細胞存活素暘性率為19.58％±4.52％,較對照組(83.26％±15.56％)、Ma組(62.50％±8.09％)及DDP組(38.67％±8.26％)降低(P＜0.05).與之相對,NS組、Ma組及DDP組caspase-3的暘性細胞率分彆為21.15％±3.68％、35.13％±10.57％、65.88％±4.81％,而Ma+DDP組較之明顯升高,為78.26％±6.09％,Ma+DDP組與其他組比較,差異均具有統計學意義(P＜0.05). 結論 Ma或DDP單用對裸鼠移植瘤具有抑製作用,Ma與DDP聯用能增彊DDP對裸鼠移植瘤的抑瘤作用和改善全身狀況,降低DDP的不良反應.其可能的作用機製是影響存活素和caspase-3的錶達,誘導腫瘤細胞凋亡.
목적 관찰고삼감(Ma)련용순박(DDP)대인간암라서이식류생장적영향병탐토기작용적가능분자궤제. 방법 장인간암세포주HepG2주입BALB/c라서액부피하건립이식류모형,대성류후,수궤분위4조:대조조、Ma조、DDP조급Ma화DDP연합조,균채용복강주사급약.기간관찰기록라서적체질량화종류체적,회제체질량변화곡선여류체생장곡선도;용약14d후처사실험라서칭류중,계산억류솔;면역조직화학법검측류조직중조망상관단백존활소여반광안산-천동안산단백매-3 (caspase-3)적표체.다조간수거비교채용단인소방차(ANOVA)분석,량조간비교채용량독립양본t검험. 결과 Ma혹DDP단용대라서이식류억류솔분별위37.5％화75.0％,Ma화DDP련용가명현억제류체생장(P＜0.05),기억류솔체83.3％,명현고우Ma혹DDP단용조.Ma+DDP조라서적평균체질량위21.50 g,비대조조(28.50 g)급Ma조(26.67 g)저,단교DDP조(17.33 g)고,차정신、활동、식량등전신상황야명현우우DDP조,류조직중세포존활소양성솔위19.58％±4.52％,교대조조(83.26％±15.56％)、Ma조(62.50％±8.09％)급DDP조(38.67％±8.26％)강저(P＜0.05).여지상대,NS조、Ma조급DDP조caspase-3적양성세포솔분별위21.15％±3.68％、35.13％±10.57％、65.88％±4.81％,이Ma+DDP조교지명현승고,위78.26％±6.09％,Ma+DDP조여기타조비교,차이균구유통계학의의(P＜0.05). 결론 Ma혹DDP단용대라서이식류구유억제작용,Ma여DDP련용능증강DDP대라서이식류적억류작용화개선전신상황,강저DDP적불량반응.기가능적작용궤제시영향존활소화caspase-3적표체,유도종류세포조망.
Objective To investigate the effect and molecular mechanism of cisplatin (DDP) combined with Matrine (Ma;plant alkaloid) against hepatocellular carcinoma using a nude mouse model with xenografted human tumors.Methods Twenty-four 6-week old male BALB/c nude mice were subcutaneously injected with HepG2 cells into the axilla,and randomly divided into four groups:control (NS) group,Ma treatment group,DDP treatment group and DDP+Ma combination treatment group.All treatments were delivered via intraperitoneal injection.Changes in whole body weights and tumor volume were assessed by before and after treatment measurements and plotting of growth curves.After 14 days of drug intervention,the mice were sacrificed for collection of tumor tissue and assessment of the tumor inhibition rates for each treatment.Affects on expression of survivin and caspase-3 were assessed by immunohistochemistry.ANOVA test and t-test were performed for the statistical analyses.Results The tumor inhibition rates for the various treatments were:37.5％,Ma alone;75.0％ DDP alone;83.3％,DDP+Ma group DDP combined.The DDP+Ma-induced inhibition was significantly greater than that achieved wit Ma or DDP alone (both P ＜ 0.05).The average weight of the DDP+Ma group (21.5 g) was lower than that of the NS group (28.5 g) and the Ma group (26.67 g),but higher than that of the DDP group (17.33 g).In addition,the DDP+Ma group also showed more robust general health,as indicated by activity,participation in life routines and appetite,than the DDP group.The rate of positive staining for survivin expression in tumor tissues was significantly lower in the DDP+Ma group (19.58％±4.52％) than in the NS group (83.26％±15.56％),the Ma group (62.50％±8.09％),and the DDP group (38.67％±8.26％) (all P ＜ 0.05).In contrast,the rate of positive staining for Bax expression was significantly higher in the DDP+Ma group (78.26％±6.09％) than in the NS group (21.15％±3.68％),the Ma group (35.13％±10.57％),and the DDP group (65.88％±4.81％) (all P ＜ 0.05).Conclusion Treatment with Ma alone or DDP alone is sufficient to inhibit the growth ofxenografted human hepatocellular carcinoma cells in nude mice.The DDP+Ma combination treatment,however,shows greater inhibitory effect,suggesting that Ma may enhance DDP's anticancer properties.The improved health status of mice treated with DDP+Ma suggests that Ma may reduce DDP toxicity.The mechanism underlying these beneficial treatment effects may involve modulation of survivin/caspase-3 expression and subsequent apoptosis.
