中华肝脏病杂志
中華肝髒病雜誌
중화간장병잡지
CHINESE JOURNAL OF HEPATOLOGY
2009年
9期
665-668
,共4页
癌%肝细胞%化学疗法%肿瘤%血管组织
癌%肝細胞%化學療法%腫瘤%血管組織
암%간세포%화학요법%종류%혈관조직
Carcinoma%hepatocellular%Chemotherapy%Neoplasms%vascular tissue
目的 探讨应用氟尿嘧啶口服新剂型S-1(替加氟、吉美嘧啶.奥替拉西按物质的量1.0:0.4:1.0构成)节拍性化学治疗抑制人高转移肝癌LCI-D20模型血管形成的作用. 方法采用治疗剂量及节拍性剂量的氟尿嘧啶口服新剂型S-1治疗30只LCI-D20模型裸鼠,分为对照组及实验A、B、C、D组.用药28 d后处死裸鼠,收集并记录肝脏、腹腔及肺的肉眼可见瘤灶,称取瘤总质量即为该裸鼠的肿瘤负荷;以鼠抗-CD34(1:50)为第一抗体,EnVision(rat)为第二抗体进行免疫组织化学染色,以肿瘤区内染成棕褐色单个内皮细胞或内皮细胞簇作为一个微血管计算,在高倍显微镜下(×400)随机计数5个视野,取平均数作为其微血管密度值-流式细胞术检测肿瘤细胞凋亡.逆转录聚合酶链反应检测肿瘤组织血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)、血小板反应蛋白-1(TSP-1)的表达.实验数据比较采用完全随机方差分析.结果 对照组及实验A、B、C、D组裸鼠瘤质量分别为(2.01±0.29)g、(0.38±0.19)g、(1.12±0.27)g、(1.38±0.33)g、(2.27±0.58)g,差异有统计学意义(F=26.36,P＜0.01);微血管密度分别为39.57±2.50、19.90±2.59、5.93±3.33,17.10±2.32、29.53±2.91,差异有统计学意义(F=43.61,P＜0.01);肿瘤组织细胞凋亡率分别为4.08%±3.20%、44.37%±2.34%、31.73%±2.52%、19.83%±0.33%、8.25%±0.57%,差异有统计学意义(F=76.76,P＜0.01).VEGFmRNA和bFGF mRNA的表达,对照组最高,A组略低,C、D组次之,B组最低;TSP-1 mRNA的表达,B组最高,C、D组略低,A组次之,对照组最低.结论 氟尿嘧啶口服新剂型S-1对肝癌LCI-D20模型有明显抑制作用;节拍性应用氟尿嘧啶口服新剂型S-1抑制肿瘤血管形成的作用明显,对肿瘤细胞的凋亡有明显促进作用,对肿瘤组织VEGF、bFGF,TSP-1的表达有调节作用.
目的 探討應用氟尿嘧啶口服新劑型S-1(替加氟、吉美嘧啶.奧替拉西按物質的量1.0:0.4:1.0構成)節拍性化學治療抑製人高轉移肝癌LCI-D20模型血管形成的作用. 方法採用治療劑量及節拍性劑量的氟尿嘧啶口服新劑型S-1治療30隻LCI-D20模型裸鼠,分為對照組及實驗A、B、C、D組.用藥28 d後處死裸鼠,收集併記錄肝髒、腹腔及肺的肉眼可見瘤竈,稱取瘤總質量即為該裸鼠的腫瘤負荷;以鼠抗-CD34(1:50)為第一抗體,EnVision(rat)為第二抗體進行免疫組織化學染色,以腫瘤區內染成棕褐色單箇內皮細胞或內皮細胞簇作為一箇微血管計算,在高倍顯微鏡下(×400)隨機計數5箇視野,取平均數作為其微血管密度值-流式細胞術檢測腫瘤細胞凋亡.逆轉錄聚閤酶鏈反應檢測腫瘤組織血管內皮生長因子(VEGF)、堿性成纖維細胞生長因子(bFGF)、血小闆反應蛋白-1(TSP-1)的錶達.實驗數據比較採用完全隨機方差分析.結果 對照組及實驗A、B、C、D組裸鼠瘤質量分彆為(2.01±0.29)g、(0.38±0.19)g、(1.12±0.27)g、(1.38±0.33)g、(2.27±0.58)g,差異有統計學意義(F=26.36,P＜0.01);微血管密度分彆為39.57±2.50、19.90±2.59、5.93±3.33,17.10±2.32、29.53±2.91,差異有統計學意義(F=43.61,P＜0.01);腫瘤組織細胞凋亡率分彆為4.08%±3.20%、44.37%±2.34%、31.73%±2.52%、19.83%±0.33%、8.25%±0.57%,差異有統計學意義(F=76.76,P＜0.01).VEGFmRNA和bFGF mRNA的錶達,對照組最高,A組略低,C、D組次之,B組最低;TSP-1 mRNA的錶達,B組最高,C、D組略低,A組次之,對照組最低.結論 氟尿嘧啶口服新劑型S-1對肝癌LCI-D20模型有明顯抑製作用;節拍性應用氟尿嘧啶口服新劑型S-1抑製腫瘤血管形成的作用明顯,對腫瘤細胞的凋亡有明顯促進作用,對腫瘤組織VEGF、bFGF,TSP-1的錶達有調節作用.
목적 탐토응용불뇨밀정구복신제형S-1(체가불、길미밀정.오체랍서안물질적량1.0:0.4:1.0구성)절박성화학치료억제인고전이간암LCI-D20모형혈관형성적작용. 방법채용치료제량급절박성제량적불뇨밀정구복신제형S-1치료30지LCI-D20모형라서,분위대조조급실험A、B、C、D조.용약28 d후처사라서,수집병기록간장、복강급폐적육안가견류조,칭취류총질량즉위해라서적종류부하;이서항-CD34(1:50)위제일항체,EnVision(rat)위제이항체진행면역조직화학염색,이종류구내염성종갈색단개내피세포혹내피세포족작위일개미혈관계산,재고배현미경하(×400)수궤계수5개시야,취평균수작위기미혈관밀도치-류식세포술검측종류세포조망.역전록취합매련반응검측종류조직혈관내피생장인자(VEGF)、감성성섬유세포생장인자(bFGF)、혈소판반응단백-1(TSP-1)적표체.실험수거비교채용완전수궤방차분석.결과 대조조급실험A、B、C、D조라서류질량분별위(2.01±0.29)g、(0.38±0.19)g、(1.12±0.27)g、(1.38±0.33)g、(2.27±0.58)g,차이유통계학의의(F=26.36,P＜0.01);미혈관밀도분별위39.57±2.50、19.90±2.59、5.93±3.33,17.10±2.32、29.53±2.91,차이유통계학의의(F=43.61,P＜0.01);종류조직세포조망솔분별위4.08%±3.20%、44.37%±2.34%、31.73%±2.52%、19.83%±0.33%、8.25%±0.57%,차이유통계학의의(F=76.76,P＜0.01).VEGFmRNA화bFGF mRNA적표체,대조조최고,A조략저,C、D조차지,B조최저;TSP-1 mRNA적표체,B조최고,C、D조략저,A조차지,대조조최저.결론 불뇨밀정구복신제형S-1대간암LCI-D20모형유명현억제작용;절박성응용불뇨밀정구복신제형S-1억제종류혈관형성적작용명현,대종류세포적조망유명현촉진작용,대종류조직VEGF、bFGF,TSP-1적표체유조절작용.
Objective To investigate the role of metronomic chemotherapy of S-1 on angiogenesis of hepatocellular carcinoma in animal model.Method S-1 was dissolved in a 0.5%(w/v)HPMC solution.(D).28 days after the treatment with 0.5%(w/v)HPMC solution,tumors in LCI-D20 mice were moved out.Tumor mass was measured and microvessel density(MVD)was used to evaluate angiogenesis in tumor.The cellular apoptosis was determined using flow cytometry.The expression of VEGE bFGF and TSP-1 was measured by RT-PCR.Results The mean tumor mass was 2.01,0.38,1.12,1.38,2.27 g in O,A,B,C,D group,respectively. The mean MVD was 39.57,19.90,5.93,17.10,29.53 in O,A,B,C,D respectively. The mean tumor cellular apoptosis rate was 4.08%,44.37%,31.73%,19.83%,and 8.25% in O,A,B,C,D respectively. The expression of VEGF and bFGF in O group was highest,and A was slightly low,and C and D raked the third place,and B was the lowst;The expression of TSP-1 in B was highest,and C and D were slightly low,and A raked the third place,and O was the Iowst. Conclusion Metronomic chemotherapy of S-1 destabilizes pre-existing tumor vasculature and inhibits ongoing angiogenesis.
