CAJ | 학술논문

目的观察合用阿司匹林(Aspirin)与索拉非尼(Sorafenib)对肝癌生长转移的抑制作用和促凋亡作用并探讨其机制.方法采用人肝癌裸鼠原位模型LCI-D20,分为对照组、Sorafenib 单用组(30 mg/kg灌胃,1d1次)、Sorafenib+ Aspirin合用组、Aspirin单用组(30 mg/kg灌胃,1 d 1 次),治疗4周后观察荷瘤小鼠生存期、肿瘤体积、肺转移,定量比较肿瘤细胞凋亡指数,观察各组荷瘤鼠生存期,检测各组核因子-κB (NF-κB)及IκBα表达.结果对照组、Sorafenib治疗组、Sorafenib + Aspirin合用组、Aspirin治疗组肿瘤体积分别为(4.76±0.51)、(1.41±0.08)、(0.66 ±0.12)和(4.58±0.47) cm3；肺转移灶数目分别为(189±21)、(96±15)、(30±17)和(92±18)个；中位生存期分别为72、98、112、80 d.肿瘤凋亡指数分别为(2.6±1.1)％、(8.6±3.7)％、(24.3±6.9)％和(6.8±1.5)％；与Sorafenib治疗组比较,Sorafenib+ Aspirin合用明显降低肿瘤体积(P＜0.05)、抑制肺转移灶数目(P＜0.01),延长荷瘤鼠生存期(P＜0.05)和促进肿瘤细胞凋亡(P＜0.05).Sorafenib 在肝癌中具有下调IκBα和上调NF-κB-p65的作用而合用Aspirin可逆转此作用.结论 Aspirin通过抑制NF-κB活化,进一步增强Sorafenib对肝癌凋亡的促进作用及对肝癌生长转移的抑制作用,并延长荷瘤鼠生存期.
목적 관찰합용아사필림(Aspirin)여색랍비니(Sorafenib)대간암생장전이적억제작용화촉조망작용병탐토기궤제.방법 채용인간암라서원위모형LCI-D20,분위대조조、Sorafenib 단용조(30 mg/kg관위,1d1차)、Sorafenib+ Aspirin합용조、Aspirin단용조(30 mg/kg관위,1 d 1 차),치료4주후관찰하류소서생존기、종류체적、폐전이,정량비교종류세포조망지수,관찰각조하류서생존기,검측각조핵인자-κB (NF-κB)급IκBα표체.결과 대조조、Sorafenib치료조、Sorafenib + Aspirin합용조、Aspirin치료조종류체적분별위(4.76±0.51)、(1.41±0.08)、(0.66 ±0.12)화(4.58±0.47) cm3；폐전이조수목분별위(189±21)、(96±15)、(30±17)화(92±18)개；중위생존기분별위72、98、112、80 d.종류조망지수분별위(2.6±1.1)％、(8.6±3.7)％、(24.3±6.9)％화(6.8±1.5)％；여Sorafenib치료조비교,Sorafenib+ Aspirin합용명현강저종류체적(P＜0.05)、억제폐전이조수목(P＜0.01),연장하류서생존기(P＜0.05)화촉진종류세포조망(P＜0.05).Sorafenib 재간암중구유하조IκBα화상조NF-κB-p65적작용이합용Aspirin가역전차작용.결론 Aspirin통과억제NF-κB활화,진일보증강Sorafenib대간암조망적촉진작용급대간암생장전이적억제작용,병연장하류서생존기.
Objective To investigate the effect of combination of sorafenib and aspirin on tumor apoptosis,tumor growth,lung metastasis and survival of tumor-beating nude mice in a highly metastatic xenograft murine model of human hepatocellular carcinoma (HCC) and explore the mechanism.Methods The Xenograft of a highly metastatic human HCC tumor (LCI-D20) was used to evaluate survival,primary tumor growth and lung metastasis after treatment with aspirin alone or in combination with sorafenib.Apoptosis of tumor cells in vivo was determined by the terminal deoxynucleotidyl-transferase mediated dUTP nick-end labeling assay (TUNEL).Results Tumor volumes were (4.76 ±0.51 ),( 1.41 ±0.08),(0.66±0.12) and (4.58 ±0.47) cm3 in control,serafenib,serafenib plus aspirin,and aspirin groups,respectively.Lung metastases were 189 ±21,96 ± 15,30 ± 17 and 92 ± 18 in four groups,and median survival was 72,98,112 and 80 days,respectively.Apoptosis rate was (2.6 ± 1.1 )％,(8.6 ±3.7)％,(24.3±6.9)％ and (6.8 ± 1.5)％ respectively in four groups.Combination of aspirin and sorafenib significantly decreased tumor volume ( P ＜ 0.05 ),inhibited number of lung metastases ( P ＜ 0.01 ),and prolonged survival (P ＜ 0.05 ) as compared with sorafenib alone group.Increased apoptosis of tumor cells (P ＜0.05 ) was observed by combination of aspirin and sorafenib.Nuclear factor-κB (NF-κB) was upregulated and IκBα was downregulated by sorafenib,which was reversed by combination of aspirin with sorafenib.Conclusion Aspirin significantly promoted apoptosis of tumor cells in combination with sorafenib through inhibiting sorafenib-induced NF-κB activation.