哈尔滨医科大学学报
哈爾濱醫科大學學報
합이빈의과대학학보
JOURNAL OF HARBIN MEDICAL UNIVERSITY
2009年
6期
539-543
,共5页
姜浩%王毓利%乔海泉%邹小龙
薑浩%王毓利%喬海泉%鄒小龍
강호%왕육리%교해천%추소룡
H_(22)肝癌细胞系%凋亡%血管密度%顺铂%长春瑞滨
H_(22)肝癌細胞繫%凋亡%血管密度%順鉑%長春瑞濱
H_(22)간암세포계%조망%혈관밀도%순박%장춘서빈
H_(22) cell line%apoptosis%vessel density%diamminedjchloroplatinum%venorelbine
目的 探讨顺铂(DDP)联合长春瑞滨(VNR)对移植性肝癌的抑制作用以及可能的分子机制.方法 建立H_(22)肝癌细胞系小鼠移植瘤模型40只,随机分为对照组、顺铂组、长春瑞滨组和顺铂+长春瑞滨组,治疗结束后第2周观察肿瘤体积变化和抑瘤率,采用脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL法)检测治疗后小鼠移植性肝癌肿瘤细胞凋亡率,应用免疫组化(S-P法)检测血管内皮生长因子(VEGF)、caspase-3、低氧诱导因子(HIF-Iα)表达及微血管密度(MVD).结果 治疗组小鼠皮下移植瘤体积和抑瘤率与对照组相比均具有统计学意义(P<0.05);DDP与VNR联合用药组与单独应用DDP或VNR相比均具有统计学意义(P<0.05).TUNEL法检测显示DDP与VNR联合用药可明显诱导肝癌细胞凋亡,与各单独用药治疗组和对照组比较均具有显著差异(P<0.05).DDP与VNR联合用药上调caspase-3,下调VEGF、HIF-Iα蛋白表达,减低MVD,与对照组比较均具有显著差异(P<0.05).结论 DDP联合VNR可明显诱导肝癌细胞凋亡发生和抑制肿瘤细胞血管化,较单独应用DDP或VNR能更有效地抑制肝癌的生长,提示DDP联合VNR在肝癌治疗中可能起到重要作用.
目的 探討順鉑(DDP)聯閤長春瑞濱(VNR)對移植性肝癌的抑製作用以及可能的分子機製.方法 建立H_(22)肝癌細胞繫小鼠移植瘤模型40隻,隨機分為對照組、順鉑組、長春瑞濱組和順鉑+長春瑞濱組,治療結束後第2週觀察腫瘤體積變化和抑瘤率,採用脫氧覈糖覈苷痠末耑轉移酶介導的缺口末耑標記法(TUNEL法)檢測治療後小鼠移植性肝癌腫瘤細胞凋亡率,應用免疫組化(S-P法)檢測血管內皮生長因子(VEGF)、caspase-3、低氧誘導因子(HIF-Iα)錶達及微血管密度(MVD).結果 治療組小鼠皮下移植瘤體積和抑瘤率與對照組相比均具有統計學意義(P<0.05);DDP與VNR聯閤用藥組與單獨應用DDP或VNR相比均具有統計學意義(P<0.05).TUNEL法檢測顯示DDP與VNR聯閤用藥可明顯誘導肝癌細胞凋亡,與各單獨用藥治療組和對照組比較均具有顯著差異(P<0.05).DDP與VNR聯閤用藥上調caspase-3,下調VEGF、HIF-Iα蛋白錶達,減低MVD,與對照組比較均具有顯著差異(P<0.05).結論 DDP聯閤VNR可明顯誘導肝癌細胞凋亡髮生和抑製腫瘤細胞血管化,較單獨應用DDP或VNR能更有效地抑製肝癌的生長,提示DDP聯閤VNR在肝癌治療中可能起到重要作用.
목적 탐토순박(DDP)연합장춘서빈(VNR)대이식성간암적억제작용이급가능적분자궤제.방법 건립H_(22)간암세포계소서이식류모형40지,수궤분위대조조、순박조、장춘서빈조화순박+장춘서빈조,치료결속후제2주관찰종류체적변화화억류솔,채용탈양핵당핵감산말단전이매개도적결구말단표기법(TUNEL법)검측치료후소서이식성간암종류세포조망솔,응용면역조화(S-P법)검측혈관내피생장인자(VEGF)、caspase-3、저양유도인자(HIF-Iα)표체급미혈관밀도(MVD).결과 치료조소서피하이식류체적화억류솔여대조조상비균구유통계학의의(P<0.05);DDP여VNR연합용약조여단독응용DDP혹VNR상비균구유통계학의의(P<0.05).TUNEL법검측현시DDP여VNR연합용약가명현유도간암세포조망,여각단독용약치료조화대조조비교균구유현저차이(P<0.05).DDP여VNR연합용약상조caspase-3,하조VEGF、HIF-Iα단백표체,감저MVD,여대조조비교균구유현저차이(P<0.05).결론 DDP연합VNR가명현유도간암세포조망발생화억제종류세포혈관화,교단독응용DDP혹VNR능경유효지억제간암적생장,제시DDP연합VNR재간암치료중가능기도중요작용.
Objective To investigate the inhibiting efficacy of combining diamminedichloroplatinum (DDP)and vinorelbine(VNR)on implanted hepatocellular carcinoma and explore its potential mechanism.Methods Fourty models of implanted hepatocellular carcinoma were constructed by H_(22) cell lines in mice firstly and were randomly divided into 4 groups including control group,DDP group,VNR group,and DDP+VNR group.The tumor volume and inhibition rate were observed in the second week after treatment.The induction of cell apoptosis was analyzed with terminal deoxynucleotidy transferase nick end labeling(TUNEL)and the expression of caspase-3,VEGF,HIF-1α and the microvascular density were detected by immunohistochemistry(S-P,streptavidin-perosidase).Results DDP group,VNR group,and DDP+VNR had smaller tumor volume and higher tumor inhibition rate(P<0.05) compared with control group,respectively and combinational therapy was more effective than either DDP or VNR strategy(P<0.05).The apoptotic index for tumors injected with DDP+VNR was significantly different from those injected with DDP,VNR and control group(P<0.05).caspase-3 was significantly up-regulated,whereas VEGF and MVD were down-regulated(P<0.05)in DDP+VNR group compared to control group,DDP group and VNR group(P<0.05).Conclusion Combination of DDP and VNR can induce cellular apoptosis and inhibit the vascularization of HCC and the growth of hepatocellular carcinoma more effectively than either DDP or VNR,which indicate that combinational therapy may play an active role in the treatment of HCC.
