中华医学杂志
中華醫學雜誌
중화의학잡지
National Medical Journal of China
2013年
6期
464-468
,共5页
郝玉琴%黄维星%冯红霞%张国惠%宁晓洪%李衡贵%郝春光%李哲海
郝玉琴%黃維星%馮紅霞%張國惠%寧曉洪%李衡貴%郝春光%李哲海
학옥금%황유성%풍홍하%장국혜%저효홍%리형귀%학춘광%리철해
癌,鳞状细胞%藜芦属%半胱氨酸天冬氨酸蛋白酶3%移植瘤%生存素
癌,鱗狀細胞%藜蘆屬%半胱氨痠天鼕氨痠蛋白酶3%移植瘤%生存素
암,린상세포%려호속%반광안산천동안산단백매3%이식류%생존소
Carcinoma,squamous cell%Veratrum%Caspase 3%Xenografts%Survivin
目的 观察白藜芦醇(Res)对人皮肤鳞状细胞癌(鳞癌)A431裸鼠移植瘤生长的影响,探讨生存素(survivin)和半胱氨酸天冬氨酸蛋白酶3(caspase-3)在此过程中的调节作用.方法 建立人皮肤鳞癌(A431)裸鼠移植瘤模型,按随机数字表法分为空白组、生理盐水阴性对照组、环磷酰胺(CTX)阳性对照组、Res高、中、低剂量组,每组10只,分别予以药物干预后处死荷瘤鼠.绘制移植瘤体积生长曲线；通过终末瘤质量,计算Res的抑瘤率；采用HE染色,观察各组移植瘤组织病理形态学变化；应用原位末端标记(TUNEL)技术检测细胞凋亡；采用Western印迹法检测Res对各组裸鼠移植瘤组织中survivin、caspase-3蛋白表达的影响.采用方差分析及Pearson相关分析对结果进行统计分析.结果 治疗结束时,(1)CTX阳性对照组、Res高、中、低剂量组、阴性对照组、空白对照组移植瘤体积分别为(1154±255)、(1002±115)、(1207±176)、(1342±211)、(1642±226)、(1564±156) mm3,瘤质量分别为(1.84±0.30)、(1.72±0.39)、(1.96±0.40)、(2.67±0.73)、(3.16±0.52)、(3.33±0.59)g,Res高、中、低剂量组瘤体积、瘤质量均低于阴性及空白对照组(均P＜0.05)；Res高、中、低剂量组抑瘤率分别为45.57％、37.97％、15.51％.(2)以上各组肿瘤组织的凋亡指数分别为36.79％±8.86％、33.15％±6.00％、18.09％±3.92％、10.53％±4.20％、3.87％±1.63％、2.73％±1.61％,Res高、中、低剂量组凋亡指数均高于阴性及空白对照组(均P＜0.05).(3)以上各组肿瘤组织中survivin蛋白相对表达量分别为0.48±0.20、0.19±0.11、0.22±0.12、0.28±0.24、0.98±0.41、0.85±0.34；caspase-3蛋白相对表达量分别为0.42±0.09、0.31±0.10、0.31±0.07、0.22±0.08、0.14±0.04、0.13±0.05,Res各组survivin蛋白的表达均低于阴性及空白对照组,caspase-3蛋白表达均高于阴性及空白对照组(均P＜0.05).(4)经Pearson相关分析,移植瘤中survivin与caspase-3蛋白表达无相关性(r=-0.279,P＞0.05).结论 Res对人皮肤鳞癌A431裸鼠移植瘤的生长具有抑制作用,其机制可能与抑制肿瘤组织中survivin的表达,进而活化caspase-3,从而诱导肿瘤细胞凋亡有关.
目的 觀察白藜蘆醇(Res)對人皮膚鱗狀細胞癌(鱗癌)A431裸鼠移植瘤生長的影響,探討生存素(survivin)和半胱氨痠天鼕氨痠蛋白酶3(caspase-3)在此過程中的調節作用.方法 建立人皮膚鱗癌(A431)裸鼠移植瘤模型,按隨機數字錶法分為空白組、生理鹽水陰性對照組、環燐酰胺(CTX)暘性對照組、Res高、中、低劑量組,每組10隻,分彆予以藥物榦預後處死荷瘤鼠.繪製移植瘤體積生長麯線；通過終末瘤質量,計算Res的抑瘤率；採用HE染色,觀察各組移植瘤組織病理形態學變化；應用原位末耑標記(TUNEL)技術檢測細胞凋亡；採用Western印跡法檢測Res對各組裸鼠移植瘤組織中survivin、caspase-3蛋白錶達的影響.採用方差分析及Pearson相關分析對結果進行統計分析.結果 治療結束時,(1)CTX暘性對照組、Res高、中、低劑量組、陰性對照組、空白對照組移植瘤體積分彆為(1154±255)、(1002±115)、(1207±176)、(1342±211)、(1642±226)、(1564±156) mm3,瘤質量分彆為(1.84±0.30)、(1.72±0.39)、(1.96±0.40)、(2.67±0.73)、(3.16±0.52)、(3.33±0.59)g,Res高、中、低劑量組瘤體積、瘤質量均低于陰性及空白對照組(均P＜0.05)；Res高、中、低劑量組抑瘤率分彆為45.57％、37.97％、15.51％.(2)以上各組腫瘤組織的凋亡指數分彆為36.79％±8.86％、33.15％±6.00％、18.09％±3.92％、10.53％±4.20％、3.87％±1.63％、2.73％±1.61％,Res高、中、低劑量組凋亡指數均高于陰性及空白對照組(均P＜0.05).(3)以上各組腫瘤組織中survivin蛋白相對錶達量分彆為0.48±0.20、0.19±0.11、0.22±0.12、0.28±0.24、0.98±0.41、0.85±0.34；caspase-3蛋白相對錶達量分彆為0.42±0.09、0.31±0.10、0.31±0.07、0.22±0.08、0.14±0.04、0.13±0.05,Res各組survivin蛋白的錶達均低于陰性及空白對照組,caspase-3蛋白錶達均高于陰性及空白對照組(均P＜0.05).(4)經Pearson相關分析,移植瘤中survivin與caspase-3蛋白錶達無相關性(r=-0.279,P＞0.05).結論 Res對人皮膚鱗癌A431裸鼠移植瘤的生長具有抑製作用,其機製可能與抑製腫瘤組織中survivin的錶達,進而活化caspase-3,從而誘導腫瘤細胞凋亡有關.
목적 관찰백려호순(Res)대인피부린상세포암(린암)A431라서이식류생장적영향,탐토생존소(survivin)화반광안산천동안산단백매3(caspase-3)재차과정중적조절작용.방법 건립인피부린암(A431)라서이식류모형,안수궤수자표법분위공백조、생리염수음성대조조、배린선알(CTX)양성대조조、Res고、중、저제량조,매조10지,분별여이약물간예후처사하류서.회제이식류체적생장곡선；통과종말류질량,계산Res적억류솔；채용HE염색,관찰각조이식류조직병리형태학변화；응용원위말단표기(TUNEL)기술검측세포조망；채용Western인적법검측Res대각조라서이식류조직중survivin、caspase-3단백표체적영향.채용방차분석급Pearson상관분석대결과진행통계분석.결과 치료결속시,(1)CTX양성대조조、Res고、중、저제량조、음성대조조、공백대조조이식류체적분별위(1154±255)、(1002±115)、(1207±176)、(1342±211)、(1642±226)、(1564±156) mm3,류질량분별위(1.84±0.30)、(1.72±0.39)、(1.96±0.40)、(2.67±0.73)、(3.16±0.52)、(3.33±0.59)g,Res고、중、저제량조류체적、류질량균저우음성급공백대조조(균P＜0.05)；Res고、중、저제량조억류솔분별위45.57％、37.97％、15.51％.(2)이상각조종류조직적조망지수분별위36.79％±8.86％、33.15％±6.00％、18.09％±3.92％、10.53％±4.20％、3.87％±1.63％、2.73％±1.61％,Res고、중、저제량조조망지수균고우음성급공백대조조(균P＜0.05).(3)이상각조종류조직중survivin단백상대표체량분별위0.48±0.20、0.19±0.11、0.22±0.12、0.28±0.24、0.98±0.41、0.85±0.34；caspase-3단백상대표체량분별위0.42±0.09、0.31±0.10、0.31±0.07、0.22±0.08、0.14±0.04、0.13±0.05,Res각조survivin단백적표체균저우음성급공백대조조,caspase-3단백표체균고우음성급공백대조조(균P＜0.05).(4)경Pearson상관분석,이식류중survivin여caspase-3단백표체무상관성(r=-0.279,P＞0.05).결론 Res대인피부린암A431라서이식류적생장구유억제작용,기궤제가능여억제종류조직중survivin적표체,진이활화caspase-3,종이유도종류세포조망유관.
Objective To explore the anti-tumor effects of resveratrol (Res) upon human skin squamous cell carcinoma A431 xenograft in nude mice and elucidate the regulatory mechanisms of survivin and caspase-3.Methods The model of human skin squamous cell carcinoma (A431) xenograft in nude mice was established.And the animals were randomly divided into saline-negative control,cyclophosphamide (CTX) positive control,Res high-,medium-and low-dosage and blank control groups (n =10 each).After drug intervention,tumor-bearing mice were sacrificed.The tumor growth curve was plotted and the Res inhibition rate calculated by terminal tumor weight.The morphological changes of tumor cell among groups were observed by hematoxylin and eosin staining; cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling TUNEL; the impact of Res upon the protein expressions of survivin and caspase-3 in tumor issues was observed by Western blot.Analysis of variance and Pearson's correlation were employed for statistical analyses.Results (1) By the end of treatment,the tumor volume of CTX,Res high-,medium-,low-dosage,saline-negative control and blank control groups were (1154 ±255),(1002 ± 115),(1207 ± 176),(1342 ± 211),(1642 ± 226),(1564 ± 156) mm3 respectively,and tumor weight of CTX,Res high-,medium-,low-dosage,saline-negative control and blank control groups (1.84 ±0.30),(1.72 ±0.39),(1.96 ± 0.40),(2.67 ± 0.73),(3.16 ±0.52),(3.33 ± 0.59) g respectively.Through analysis of variance,the tumor volume and weight of Res high-,medium-,low-dosage groups were smaller than those of saline-negative control and blank control groups (all P ＜ 0.05).The inhibition rate of Res high-,medium-and low-dosage groups were 45.57％,37.97％ and 15.51％ respectively.(2) The apoptosis index of the above groups were 36.79％ ± 8.86％,33.15％ ± 6.00％,18.09％ ±3.92％,10.53％ ±4.20％,3.87％ ± 1.63％,2.73％ ± 1.61％.Through analysis of variance,the apoptosis index of Res groups were higher than those of saline-negative control and blank control groups (all P ＜ 0.05).(3) The protein expression of survivin/β-actin of each group were 0.48 ± 0.20,0.19 ±0.11,0.22 ±0.12,0.28 ±0.24,0.98 ±0.41,0.85 ±0.34.The protein expression of caspase-3/β-actin of each group were0.42±0.09,0.31±0.10,0.31±0.07,0.22±0.08,0.14±0.04,0.13±0.05respectively.Through analysis of variance,the protein expression of survivin of Res groups was lower than those of the saline-negative control and blank control groups (all P ＜ 0.05).And the protein expression of caspase-3 of Res groups were higher than those of the saline-negative control and blank control group (all P ＜ 0.05).Through Pearson's analysis,the protein expression of survivin and caspase-3 had no correlation (r =-0.279,P ＞ 0.05).Conclusions Res inhibits the growth of human skin squamous cell carcinoma A431 xenograft in nude mice.And its mechanism may be associated with the apoptosis of tumor cell through the depression of survivin and the activation of caspase-3.
