中华实验外科杂志
中華實驗外科雜誌
중화실험외과잡지
CHINESE JOURNAL OF EXPERIMENTAL SURGERY
2012年
4期
643-645
,共3页
癌,肝细胞%索拉非尼%5-氟尿嘧啶%细胞外信号调节激酶
癌,肝細胞%索拉非尼%5-氟尿嘧啶%細胞外信號調節激酶
암,간세포%색랍비니%5-불뇨밀정%세포외신호조절격매
Carcinoma,hepatocellular%Sorafenib%Fluorouracil%Extracellular signal-regulated kinase
目的 观察索拉非尼对人肝癌高转移细胞HCCLM3多药耐药蛋白表达的抑制作用及其与5-氟尿嘧啶(5-Fu)联用的协同效应.方法 使用索拉非尼和/或5-Fu对HCCLM3细胞进行干预后,应用免疫细胞化学方法、Western blot法分别检测细胞中磷酸化细胞外信号调节激酶(pERK)及耐药蛋白渗透性糖蛋白(P-gp)和拓扑异构酶2A(TOP-2α)的表达；将HCCLM3细胞接种于裸鼠皮下,并进行药物干预治疗,通过观察肿瘤体积的变化,评估药物对肿瘤生长的抑制作用.细胞实验及裸鼠实验均设置对照组(C)、索拉非尼组(S)、5-Fu组(F)、索拉非尼与5-Fu联用组(SF).结果 各组细胞的pERK、P-gp及TOP-2α表达分别为:C组(0.061 ±0.026、0.076±0.033、0.075±0.022)、S组(0.024±0.011、0.027±0.006、0.025±0.024)、F组(0.080±0.036、0.047±0.005、0.059±0.025)、SF组(0.027±0.015、0.022±0.019、0.038±0.020).与C组比较,S组和SF组的pERK、P-gp、TOP-2α的表达明显下降(P＜0.05).各组裸鼠皮下瘤体积(cm3)分别为:C组(5.292±1.523)、S组(1.620 ±0.784)、SF组(1.1100.402)、F组(4.327±1.709).与C组比较,S组和SF组裸鼠的肿瘤体积明显缩小(P＜0.05).结论 索拉非尼单独或与5-Fu联用能明显抑制HCCLM3细胞中pERK、P-gp、TOP-2α蛋白的表达及裸鼠皮下瘤的生长.
目的 觀察索拉非尼對人肝癌高轉移細胞HCCLM3多藥耐藥蛋白錶達的抑製作用及其與5-氟尿嘧啶(5-Fu)聯用的協同效應.方法 使用索拉非尼和/或5-Fu對HCCLM3細胞進行榦預後,應用免疫細胞化學方法、Western blot法分彆檢測細胞中燐痠化細胞外信號調節激酶(pERK)及耐藥蛋白滲透性糖蛋白(P-gp)和拓撲異構酶2A(TOP-2α)的錶達；將HCCLM3細胞接種于裸鼠皮下,併進行藥物榦預治療,通過觀察腫瘤體積的變化,評估藥物對腫瘤生長的抑製作用.細胞實驗及裸鼠實驗均設置對照組(C)、索拉非尼組(S)、5-Fu組(F)、索拉非尼與5-Fu聯用組(SF).結果 各組細胞的pERK、P-gp及TOP-2α錶達分彆為:C組(0.061 ±0.026、0.076±0.033、0.075±0.022)、S組(0.024±0.011、0.027±0.006、0.025±0.024)、F組(0.080±0.036、0.047±0.005、0.059±0.025)、SF組(0.027±0.015、0.022±0.019、0.038±0.020).與C組比較,S組和SF組的pERK、P-gp、TOP-2α的錶達明顯下降(P＜0.05).各組裸鼠皮下瘤體積(cm3)分彆為:C組(5.292±1.523)、S組(1.620 ±0.784)、SF組(1.1100.402)、F組(4.327±1.709).與C組比較,S組和SF組裸鼠的腫瘤體積明顯縮小(P＜0.05).結論 索拉非尼單獨或與5-Fu聯用能明顯抑製HCCLM3細胞中pERK、P-gp、TOP-2α蛋白的錶達及裸鼠皮下瘤的生長.
목적 관찰색랍비니대인간암고전이세포HCCLM3다약내약단백표체적억제작용급기여5-불뇨밀정(5-Fu)련용적협동효응.방법 사용색랍비니화/혹5-Fu대HCCLM3세포진행간예후,응용면역세포화학방법、Western blot법분별검측세포중린산화세포외신호조절격매(pERK)급내약단백삼투성당단백(P-gp)화탁복이구매2A(TOP-2α)적표체；장HCCLM3세포접충우라서피하,병진행약물간예치료,통과관찰종류체적적변화,평고약물대종류생장적억제작용.세포실험급라서실험균설치대조조(C)、색랍비니조(S)、5-Fu조(F)、색랍비니여5-Fu련용조(SF).결과 각조세포적pERK、P-gp급TOP-2α표체분별위:C조(0.061 ±0.026、0.076±0.033、0.075±0.022)、S조(0.024±0.011、0.027±0.006、0.025±0.024)、F조(0.080±0.036、0.047±0.005、0.059±0.025)、SF조(0.027±0.015、0.022±0.019、0.038±0.020).여C조비교,S조화SF조적pERK、P-gp、TOP-2α적표체명현하강(P＜0.05).각조라서피하류체적(cm3)분별위:C조(5.292±1.523)、S조(1.620 ±0.784)、SF조(1.1100.402)、F조(4.327±1.709).여C조비교,S조화SF조라서적종류체적명현축소(P＜0.05).결론 색랍비니단독혹여5-Fu련용능명현억제HCCLM3세포중pERK、P-gp、TOP-2α단백적표체급라서피하류적생장.
Objective To explore the inhibitory effect of sorafenib on the expression of multidrug resistance proteins in HCCLM3,a human hepatocellular carcinoma cell line with high metastatic potential,and to investigate the synergistic effects of sorafenib and fluorouracil (5-Fu).Methods The HCCLM3 cells were treated with sorafenib plus 5-Fu or alone,respectively,and mock-treated as negative control.The expression of phosphorylated extracellular signal-regulated kinase ( pERK),P-glycoprotein (P-gp) and topoisomerase 2α(TOP-2α) in these cells was analyzed by immunocytochemistry and Western blotting.Moreover,nude mice were subcutaneously inoculated with HCCLM3 cells,and drug intervention was conducted similarly in four groups as described above.The changes in tumor volume were monitored.3 treatment groups and I control group were established in both cell and nude mice experiment:negative control (C),sorafenib (S),sorafenib and 5-Fu (SF),5-Fu (F).Results In the cell experiment,the quantified protein expression levels of pERK,P-gp and TOP-2α after normalization were as follows:C group (0.061 ± 0.026,0.076 ± 0.033,0.075 ± 0.022),S group (0.024 0.011,0.027 ± 0.006,0.025 ±0.024),SF group (0.027 ±0.015,0.022 ±0.019,0.038 ±0.020),F group (0.080 ± 0.036,0.047± 0.005,0.059 ± 0.025 ).Statistically,the cellular expression of pERK,P-gp and TOP-2α in S and SF groups was significantly reduced as compared with C group (P ＜ 0.05 ).In the nude mice experiment,the volume ( cm3 ) of tumors was as follows:C group ( 5.292 ± 1.523),S group ( 1.620 ± 0.784),SF group ( 1.110 ±0.402),F group (4.327± 1.709).Statistically,the volume of tumors in S and SF groups was significantly less than that in C group (P ＜ 0.05 ).Conclusion Sorafenib or the combination of sorafenib and 5-Fu can reduce not only the expression of pERK,P-gp and TOP-2α in HCCLM3 cells significantly,but also the volume of tumors in nude mice as well.
