三氧化二砷对人宫颈癌裸鼠皮下移植瘤的抗肿瘤作用及机制研究
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摘要
目的探讨不同剂量三氧化二砷As2O3对人宫颈癌hela细胞株裸鼠皮下移植瘤的抗肿瘤作用及机制。
方法将4×106个hela细胞接种于裸鼠皮下,建立人宫颈癌裸鼠皮下移植瘤模型,随机分为As2O3低、中、高剂量组、空白对照组(生理盐水)及阳性对照组(顺铂),腹腔连续给药10d,停药后24h处死裸鼠留取标本计算抑瘤率,检测血常规及肝肾功能,流式细胞仪检测凋亡率,荧光定量PCR (RT-PCR)检测caspase-3基因的相对表达量,免疫组化(SP)法检测p-ERK的表达。
结果As203可抑制宫颈癌移植瘤的生长,低剂量As203组及DDP组抑瘤率分别为46.07%和70.34%,与生理盐水组相比均有统计学意义(P<0.05)；高、中、低剂量As203组流式细胞仪检测时均出现典型凋亡峰,凋亡率分别为17.89%、17.19%、18.52%：As203作用后caspase-3基因的表达较生理盐水组升高,差异有统计学意义(P<0.05)；各剂量As2O3组较生理盐水组p-ERK的表达降低；As2O3组与DDP组相比,未表现出明显的血液学及肝、肾毒性。
结论As203对人宫颈癌移植瘤的生长具有明显的抑制作用,其机制与上调caspase-3基因的表达诱导细胞凋亡,下调p-ERK的表达抑制MAPK信号传导通路有关。
Objective:To study the anti-tumor effect and mechanism of arsenic trioxide on different concentration on the subcutaneously transplantable tumor of human cervical hela cell in nude mice in vivo.
Methods:Nude mice were implanted with 4×106 cervical hela cell,Then they were divided at random into five groups:different concentration As2O3, saline and DDP group, which received intraperitoneal injection for ten days. The tumor inhibition rate was calculated to evaluate the anti-tumor effect..Liver、kidney function and the blood were tested. The apoptosis rate was detected by the flow cytometer.The relative expression of caspase-3 were detected by the Reverse transcription-polymerase chain reaction. Immunohistochemistry SP method was adopted to detect the expression of p-ERK.
Results:Arsenic trioxide can inhibie the growth of the transplanted tumor.1.0mg/kg As2O3 and DDP groups could obviously inhibit the growth of transplantable tumor with the tumor inhibitory rate of 46.07% and 70.34% respectively. In contrast to the saline, the difference was significant(P<0.05)。In thel.Omg/kg As2O3 compared with the saline the expression of caspase-3 was up-regulated, with statistically differences (P<0.05); the expression of p-ERK between As2O3 groups and saline was down-regulated; As2O3 group compared with the DDP, did not show obvious hematology、hepatic and nephritic toxicity.
Conclusion:As2O3 can inhibit the growth of the human cervical subcutaneous transplantable tumor by regulating up the expression of caspase-3 and inducing the cell apoptosis and regulating down the expression of p-ERK.
方法将4×106个hela细胞接种于裸鼠皮下,建立人宫颈癌裸鼠皮下移植瘤模型,随机分为As2O3低、中、高剂量组、空白对照组(生理盐水)及阳性对照组(顺铂),腹腔连续给药10d,停药后24h处死裸鼠留取标本计算抑瘤率,检测血常规及肝肾功能,流式细胞仪检测凋亡率,荧光定量PCR (RT-PCR)检测caspase-3基因的相对表达量,免疫组化(SP)法检测p-ERK的表达。
结果As203可抑制宫颈癌移植瘤的生长,低剂量As203组及DDP组抑瘤率分别为46.07%和70.34%,与生理盐水组相比均有统计学意义(P<0.05)；高、中、低剂量As203组流式细胞仪检测时均出现典型凋亡峰,凋亡率分别为17.89%、17.19%、18.52%：As203作用后caspase-3基因的表达较生理盐水组升高,差异有统计学意义(P<0.05)；各剂量As2O3组较生理盐水组p-ERK的表达降低；As2O3组与DDP组相比,未表现出明显的血液学及肝、肾毒性。
结论As203对人宫颈癌移植瘤的生长具有明显的抑制作用,其机制与上调caspase-3基因的表达诱导细胞凋亡,下调p-ERK的表达抑制MAPK信号传导通路有关。
Objective:To study the anti-tumor effect and mechanism of arsenic trioxide on different concentration on the subcutaneously transplantable tumor of human cervical hela cell in nude mice in vivo.
Methods:Nude mice were implanted with 4×106 cervical hela cell,Then they were divided at random into five groups:different concentration As2O3, saline and DDP group, which received intraperitoneal injection for ten days. The tumor inhibition rate was calculated to evaluate the anti-tumor effect..Liver、kidney function and the blood were tested. The apoptosis rate was detected by the flow cytometer.The relative expression of caspase-3 were detected by the Reverse transcription-polymerase chain reaction. Immunohistochemistry SP method was adopted to detect the expression of p-ERK.
Results:Arsenic trioxide can inhibie the growth of the transplanted tumor.1.0mg/kg As2O3 and DDP groups could obviously inhibit the growth of transplantable tumor with the tumor inhibitory rate of 46.07% and 70.34% respectively. In contrast to the saline, the difference was significant(P<0.05)。In thel.Omg/kg As2O3 compared with the saline the expression of caspase-3 was up-regulated, with statistically differences (P<0.05); the expression of p-ERK between As2O3 groups and saline was down-regulated; As2O3 group compared with the DDP, did not show obvious hematology、hepatic and nephritic toxicity.
Conclusion:As2O3 can inhibit the growth of the human cervical subcutaneous transplantable tumor by regulating up the expression of caspase-3 and inducing the cell apoptosis and regulating down the expression of p-ERK.
引文
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