西安交通大学学报(医学版)
西安交通大學學報(醫學版)
서안교통대학학보(의학판)
JOURNAL OF XI'AN JIAOTONG UNIVERSITY(MEDICAL SCIENCES)
2015年
4期
467-471
,共5页
吴丽贤%黄立森%陈瑞家%田崛%柯方
吳麗賢%黃立森%陳瑞傢%田崛%柯方
오려현%황립삼%진서가%전굴%가방
皮下荷瘤%survivin 反义核酸%紫杉醇%联合用药%细胞凋亡
皮下荷瘤%survivin 反義覈痠%紫杉醇%聯閤用藥%細胞凋亡
피하하류%survivin 반의핵산%자삼순%연합용약%세포조망
subcutaneous tumor bearing%survivin antisense nucleic acid%taxol%combined therapy%cell apoptosis
目的:研究 survivin 反义核酸与紫杉醇联合应用对皮下荷瘤 Bal b/c 小鼠模型的治疗作用,并初步探讨对其抗癌作用的机制。方法在 Bal b/c 小鼠皮下注射 C26细胞,建立皮下瘤模型,采用瘤内注射的方式,将实验分空白组(C)、lipo2000对照组(L)、紫杉醇组(T)、survivin 反义核酸组(A)、survivin 反义核酸联合紫杉醇组(A+T)5个不同组,观察肿瘤的生长状态,TUNEL 法检测凋亡细胞,Western blot 法检测 survivin 蛋白表达。结果①各治疗组均达到了(T/C)<60%,与 L 组比较差异有统计学意义(P <0.05),体内证实给药干预有效;小鼠瘤重的抑瘤率结果显示,与 C 组比较,T、A、A+T 各给药组均能抑制小鼠瘤重,差异具有统计学意义(P <0.05),从抑制肿瘤质量增长方面而言,二者联合用药[瘤重抑瘤率为(54.16±0.32)%]将紫杉醇[瘤重抑瘤率为(21.82±0.84)%]的抗癌活性提高了59%以上;②TUNEL 法检测凋亡细胞:空白对照组几乎没有肿瘤细胞凋亡。T 组及 A 组有一定量的凋亡细胞,以上试验结果提示,紫杉醇具有促进肿瘤细胞凋亡的能力,A+T 不仅加强了对肿瘤细胞的杀伤作用,而且二者的协同作用可能对肿瘤耐药性有所影响,最终使得其促肿瘤细胞凋亡的作用尤为显著;③survivin 蛋白表达:结果显示,A+T组 survivin 蛋白的表达明显降低,而不影响β-actin 的表达,C 组和 L 组相比无明显变化,T 组、A 组、A+T 组 A 值的比值分别为0.895±0.011、0.704±0.121、0.345±0.019,经方差分析,A+T 组与 C、L、A、T 组的表达量差异具有统计学意义(P <0.05)。结论survivin 反义核酸与紫杉醇联合用药,可能通过下调 survivin 蛋白的表达从而促进肿瘤细胞凋亡,联合用药可降低机体耐药性,发挥协同作用。
目的:研究 survivin 反義覈痠與紫杉醇聯閤應用對皮下荷瘤 Bal b/c 小鼠模型的治療作用,併初步探討對其抗癌作用的機製。方法在 Bal b/c 小鼠皮下註射 C26細胞,建立皮下瘤模型,採用瘤內註射的方式,將實驗分空白組(C)、lipo2000對照組(L)、紫杉醇組(T)、survivin 反義覈痠組(A)、survivin 反義覈痠聯閤紫杉醇組(A+T)5箇不同組,觀察腫瘤的生長狀態,TUNEL 法檢測凋亡細胞,Western blot 法檢測 survivin 蛋白錶達。結果①各治療組均達到瞭(T/C)<60%,與 L 組比較差異有統計學意義(P <0.05),體內證實給藥榦預有效;小鼠瘤重的抑瘤率結果顯示,與 C 組比較,T、A、A+T 各給藥組均能抑製小鼠瘤重,差異具有統計學意義(P <0.05),從抑製腫瘤質量增長方麵而言,二者聯閤用藥[瘤重抑瘤率為(54.16±0.32)%]將紫杉醇[瘤重抑瘤率為(21.82±0.84)%]的抗癌活性提高瞭59%以上;②TUNEL 法檢測凋亡細胞:空白對照組幾乎沒有腫瘤細胞凋亡。T 組及 A 組有一定量的凋亡細胞,以上試驗結果提示,紫杉醇具有促進腫瘤細胞凋亡的能力,A+T 不僅加彊瞭對腫瘤細胞的殺傷作用,而且二者的協同作用可能對腫瘤耐藥性有所影響,最終使得其促腫瘤細胞凋亡的作用尤為顯著;③survivin 蛋白錶達:結果顯示,A+T組 survivin 蛋白的錶達明顯降低,而不影響β-actin 的錶達,C 組和 L 組相比無明顯變化,T 組、A 組、A+T 組 A 值的比值分彆為0.895±0.011、0.704±0.121、0.345±0.019,經方差分析,A+T 組與 C、L、A、T 組的錶達量差異具有統計學意義(P <0.05)。結論survivin 反義覈痠與紫杉醇聯閤用藥,可能通過下調 survivin 蛋白的錶達從而促進腫瘤細胞凋亡,聯閤用藥可降低機體耐藥性,髮揮協同作用。
목적:연구 survivin 반의핵산여자삼순연합응용대피하하류 Bal b/c 소서모형적치료작용,병초보탐토대기항암작용적궤제。방법재 Bal b/c 소서피하주사 C26세포,건립피하류모형,채용류내주사적방식,장실험분공백조(C)、lipo2000대조조(L)、자삼순조(T)、survivin 반의핵산조(A)、survivin 반의핵산연합자삼순조(A+T)5개불동조,관찰종류적생장상태,TUNEL 법검측조망세포,Western blot 법검측 survivin 단백표체。결과①각치료조균체도료(T/C)<60%,여 L 조비교차이유통계학의의(P <0.05),체내증실급약간예유효;소서류중적억류솔결과현시,여 C 조비교,T、A、A+T 각급약조균능억제소서류중,차이구유통계학의의(P <0.05),종억제종류질량증장방면이언,이자연합용약[류중억류솔위(54.16±0.32)%]장자삼순[류중억류솔위(21.82±0.84)%]적항암활성제고료59%이상;②TUNEL 법검측조망세포:공백대조조궤호몰유종류세포조망。T 조급 A 조유일정량적조망세포,이상시험결과제시,자삼순구유촉진종류세포조망적능력,A+T 불부가강료대종류세포적살상작용,이차이자적협동작용가능대종류내약성유소영향,최종사득기촉종류세포조망적작용우위현저;③survivin 단백표체:결과현시,A+T조 survivin 단백적표체명현강저,이불영향β-actin 적표체,C 조화 L 조상비무명현변화,T 조、A 조、A+T 조 A 치적비치분별위0.895±0.011、0.704±0.121、0.345±0.019,경방차분석,A+T 조여 C、L、A、T 조적표체량차이구유통계학의의(P <0.05)。결론survivin 반의핵산여자삼순연합용약,가능통과하조 survivin 단백적표체종이촉진종류세포조망,연합용약가강저궤체내약성,발휘협동작용。
Objective To explore the therapeutic effects of combined application of survivin antisense nucleic acid and taxol in subcutaneous xenograft mouse model of Balb/c and to preliminarily investigate the mechanism of the anticancer effects.Methods The model of subcutaneous tumor was established by hypodermic injection of C26 cells into Bal b/c mice.The mice were then randomly divided into five groups through the internal tumor injection:the blank group (C),lipo2000 group (L),paclitaxel group (T),survivin antisense nucleic acid group (A),and survivin antisense nucleic acid combined with paclitaxel group (A+T).We observed tumor growth,determined cell apoptosis by TUNEL method,and detected the expression of survivin by Western blot.Results ① All treatment groups had T/C<60%,which was significantly different from that of group L (P <0.05);the intervention was proved effective in vivo .The tumor inhibition rate of mice tumor weight showed that there were significantly curative effects in groups T,A and A+ T compared with that in group C (P < 0.05 ).The antitumor activity of paclitaxel (tumor inhibition rate of 21.82%±0.84%)could be improved by more than 59% through combination therapy (tumor inhibition rate of 54.1 6% ± 0.32%)concerning inhibition of tumor weight growth.② TUNEL method detected apoptotic cells:The tumor cells hardly had apoptosis in the blank group while T group and A group had a certain number of apoptotic cells.The experiment results suggested that PTX could promote tumor cell apoptosis,and that not only A+T strengthened the effect in killing tumor cells,but also the synergy of both could influence tumor resistance and ultimately make the effect in promoting tumor cell apoptosis conspicuous.③ The expression of survivin protein:The results showed that the expression of survivin protein in group A + T was obviously decreased without the expression of β-actin affected;it did not change significantly in group C compared with group L.The ratio of the A-value in groups T,A and A+T was 0.895 ±0.01 1,0.704 ±0.121 and 0.345 ± 0.01 9,respectively.Analysis of variance t-test showed that the expression level in group A+T obviously differed from that in groups C,L,A and T (P <0.05).Conclusion The combined therapy of survivin antisense nucleic acid and taxol can promote tumor cell apoptosis by downregulating the expression of survivin protein,reduce the body’s resistance to drugs and create synergetic effects.