中华肿瘤杂志
中華腫瘤雜誌
중화종류잡지
CHINESE JOURNAL OF ONCOLOGY
2013年
2期
98-102
,共5页
肝肿瘤%索拉非尼%氟尿嘧啶%磷酸化胞外信号调节激酶%P-糖蛋白%拓扑异构酶Ⅱa%小鼠,裸
肝腫瘤%索拉非尼%氟尿嘧啶%燐痠化胞外信號調節激酶%P-糖蛋白%拓撲異構酶Ⅱa%小鼠,裸
간종류%색랍비니%불뇨밀정%린산화포외신호조절격매%P-당단백%탁복이구매Ⅱa%소서,라
Liver neoplasms%Sorafenib%Fluorouracil%Phosphorylated extracellular signal-regulated kinase%P-glycoprotein%Topoisomerase 2-alpha%Mice nude
目的 观察索拉非尼联合氟尿嘧啶(5-Fu)对荷人肝癌裸鼠肿瘤的生长和肺转移的抑制作用,并探讨其作用机制.方法 选用人肝癌细胞系HCCLM3制成人肝癌裸鼠模型.将裸鼠分为对照组、索拉非尼组、5-Fu组和索拉非尼+5-Fu组,检测各组荷人肝癌裸鼠肿瘤重量和肺转移数目,采用免疫组织化学和Western blot方法检测肿瘤组织中磷酸化胞外信号调节激酶(p-ERK)、P-糖蛋白(P-gp)和拓扑异构酶Ⅱa(Topo Ⅱa)蛋白的表达.结果 对照组、索拉非尼组、5-Fu组和索拉非尼+5-Fu组裸鼠的肿瘤重量分别为(2.700 ±0.825)g、(0.933±0.333)g、(2.438 ±0.793)g和(0.786±0.212)g,其中索拉非尼组和索拉非尼+ 5-Fu组与对照组比较,差异均有统计学意义(均P＜0.05).对照组、索拉非尼组、5-Fu组和索拉非尼+5-Fu组裸鼠肺转移数分别为(12.714±6.317)个、(4.333±3.983)个、(10.429±6.241)个和(5.429 ±4.315)个,其中索拉非尼组和索拉非尼+5-Fu组裸鼠肺转移数明显低于对照组和5-Fu组(均P＜0.05).对照组、索拉非尼组、5-Fu组、索拉非尼+5-Fu组肿瘤组织中p-ERK蛋白的相对表达量分别为0.017±0.010、0.010±0.008、0.018±0.009和0.011±0.007,P-gp蛋白的相对表达量分别为0.085±0.012、0.044±0.020、0.063±0.032和0.044±0.023,TopoⅡa蛋白的相对表达量分别为0.103±0.093、0.020±0.018、0.065±0.034和0.062±0.026.与对照组比较,索拉非尼组肿瘤组织中p-ERK、P-gp和TopoⅡa蛋白的表达明显下降(P＜0.05).结论 索拉非尼能明显抑制荷人肝癌裸鼠肿瘤的生长和肺转移,抑制肿瘤组织中P-gp和TopoⅡa蛋白的表达.与索拉非尼组比较,索拉非尼+ 5-Fu组对p-ERK、P-gp和TopoⅡa蛋白表达的抑制无明显优势.
目的 觀察索拉非尼聯閤氟尿嘧啶(5-Fu)對荷人肝癌裸鼠腫瘤的生長和肺轉移的抑製作用,併探討其作用機製.方法 選用人肝癌細胞繫HCCLM3製成人肝癌裸鼠模型.將裸鼠分為對照組、索拉非尼組、5-Fu組和索拉非尼+5-Fu組,檢測各組荷人肝癌裸鼠腫瘤重量和肺轉移數目,採用免疫組織化學和Western blot方法檢測腫瘤組織中燐痠化胞外信號調節激酶(p-ERK)、P-糖蛋白(P-gp)和拓撲異構酶Ⅱa(Topo Ⅱa)蛋白的錶達.結果 對照組、索拉非尼組、5-Fu組和索拉非尼+5-Fu組裸鼠的腫瘤重量分彆為(2.700 ±0.825)g、(0.933±0.333)g、(2.438 ±0.793)g和(0.786±0.212)g,其中索拉非尼組和索拉非尼+ 5-Fu組與對照組比較,差異均有統計學意義(均P＜0.05).對照組、索拉非尼組、5-Fu組和索拉非尼+5-Fu組裸鼠肺轉移數分彆為(12.714±6.317)箇、(4.333±3.983)箇、(10.429±6.241)箇和(5.429 ±4.315)箇,其中索拉非尼組和索拉非尼+5-Fu組裸鼠肺轉移數明顯低于對照組和5-Fu組(均P＜0.05).對照組、索拉非尼組、5-Fu組、索拉非尼+5-Fu組腫瘤組織中p-ERK蛋白的相對錶達量分彆為0.017±0.010、0.010±0.008、0.018±0.009和0.011±0.007,P-gp蛋白的相對錶達量分彆為0.085±0.012、0.044±0.020、0.063±0.032和0.044±0.023,TopoⅡa蛋白的相對錶達量分彆為0.103±0.093、0.020±0.018、0.065±0.034和0.062±0.026.與對照組比較,索拉非尼組腫瘤組織中p-ERK、P-gp和TopoⅡa蛋白的錶達明顯下降(P＜0.05).結論 索拉非尼能明顯抑製荷人肝癌裸鼠腫瘤的生長和肺轉移,抑製腫瘤組織中P-gp和TopoⅡa蛋白的錶達.與索拉非尼組比較,索拉非尼+ 5-Fu組對p-ERK、P-gp和TopoⅡa蛋白錶達的抑製無明顯優勢.
목적 관찰색랍비니연합불뇨밀정(5-Fu)대하인간암라서종류적생장화폐전이적억제작용,병탐토기작용궤제.방법 선용인간암세포계HCCLM3제성인간암라서모형.장라서분위대조조、색랍비니조、5-Fu조화색랍비니+5-Fu조,검측각조하인간암라서종류중량화폐전이수목,채용면역조직화학화Western blot방법검측종류조직중린산화포외신호조절격매(p-ERK)、P-당단백(P-gp)화탁복이구매Ⅱa(Topo Ⅱa)단백적표체.결과 대조조、색랍비니조、5-Fu조화색랍비니+5-Fu조라서적종류중량분별위(2.700 ±0.825)g、(0.933±0.333)g、(2.438 ±0.793)g화(0.786±0.212)g,기중색랍비니조화색랍비니+ 5-Fu조여대조조비교,차이균유통계학의의(균P＜0.05).대조조、색랍비니조、5-Fu조화색랍비니+5-Fu조라서폐전이수분별위(12.714±6.317)개、(4.333±3.983)개、(10.429±6.241)개화(5.429 ±4.315)개,기중색랍비니조화색랍비니+5-Fu조라서폐전이수명현저우대조조화5-Fu조(균P＜0.05).대조조、색랍비니조、5-Fu조、색랍비니+5-Fu조종류조직중p-ERK단백적상대표체량분별위0.017±0.010、0.010±0.008、0.018±0.009화0.011±0.007,P-gp단백적상대표체량분별위0.085±0.012、0.044±0.020、0.063±0.032화0.044±0.023,TopoⅡa단백적상대표체량분별위0.103±0.093、0.020±0.018、0.065±0.034화0.062±0.026.여대조조비교,색랍비니조종류조직중p-ERK、P-gp화TopoⅡa단백적표체명현하강(P＜0.05).결론 색랍비니능명현억제하인간암라서종류적생장화폐전이,억제종류조직중P-gp화TopoⅡa단백적표체.여색랍비니조비교,색랍비니+ 5-Fu조대p-ERK、P-gp화TopoⅡa단백표체적억제무명현우세.
Objective The aim of this study was to explore the inhibitory effect of sorafenib and 5-Fu on transplanted human liver cancer in nude mice,and to investigate the synergistic effect and mechanism between sorafenib and 5-Fu.Methods The nude mouse model of human liver cancer was made by transplantation of human highly metastatic liver cancer cell line HCCLM3 cells,and the tumor-bearing nude mice were treated with sorafenib,5-Fu or both,respectively,and mock-treated tumor-beating nude mice as negative control.To assess the anti-tumor effect of sorafenib and the synergistic effect of sorafenib combined with 5-Fu by measuring the tumor weight and number of lung metastases.Moreover,the expressions of phosphorylated extracellular signal-regulated kinase (p-ERK),P-glycoprotein (P-gp) and topoisomerase 2-alpha (Topo Ⅱa) in the nude mice were assayed by immunocytochemistry and Western blot.Results The tumor weights and numbers of lung metastases were: (2.7 ± 0.825) g and 12.714 ± 6.317 in the negative control group,(0.933 ± 0.333) g and 4.333 ± 3.983 in the sorafenib group,(0.786 ± 0.212) g and 5.429 ±4.315 in the Sorafenib +5-Fu combination group,and (2.438 ± 0.793)g and 10.429 ± 6.241 in the 5-Fu group.Statistically,the tumor weights and numbers of lung metastases in the sorafenib group and combination group were significantly decreased,compared with that in the control group (P ＜ 0.05).There was no significant difference in the tumor weight and number of lung metastases between the sorafenib group and the combination treatment group (P ＞ 0.05).The expression levels of p-ERK,P-gp and Topo Ⅱ a proteins in the tumors after normalization were: negative control (0.017 ±0.010,0.085 ± 0.012,0.103 ± 0.093),sorafenib group (0.010 ±0.008,0.044 ±0.020,0.020 ±0.018),combination group (0.011 ±0.007,0.043 ±0.023,0.062 ±0.026),and 5-Fu group (0.018 ±0.009,0.063 ±0.032,0.065 ± 0.034),respectively.Statistically,the expression of p-ERK,P-gp and Topo Ⅱ a in the Sorafenib group was significantly reduced compared with that of the control group (P ＜ 0.05),and there was no significant difference in the expression of p-ERK,P-gp and Topo Ⅱ a between the sorafenib group and the combination treatment group (P ＞ 0.05).Conclusions Sorafenib can inhibit not only the tumor growth and lung metastsis in the nude mouse models,but also reduce the expression of multidrug resistance proteins P-gp and Topo Ⅱ a as well.There is no significant advantage for the sorafenib + 5-Fu combination treatment than Sorafenib alone in inhibiting the expression of p-ERK,P-gp and Topo Ⅱ a.
