人参皂苷Rh2对荷结肠癌CT-26小鼠抗瘤作用及免疫指标的影响
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摘要
目的：研究人参皂苷Rh2对荷瘤小鼠抗肿瘤作用及对免疫指标的影响,寻求抗肿瘤作用强而毒副作用小的中药有效成分。
方法：首先进行肿瘤细胞系的培养传代。肿瘤细胞培养至一定数量时,用胰蛋白酶消化重悬,制备成肿瘤细胞悬液,接种于32只健康雌雄各半BALB/c小鼠右侧颈背部皮下,建立荷小鼠结肠癌CT-26动物模型。2周后动物肿瘤模型已稳定,除正常对照组外,将成瘤均匀且肿瘤大小相近的24只荷瘤小鼠模型随机分成3组：0.4%乙醇灌胃对照组、人参皂苷Rh2(0.4%乙醇混悬液)灌胃治疗组、5-FU腹腔注射治疗组。治疗21天后,各组小鼠称重,摘取小鼠眼球,收集血液标本,静置离心后吸取上层血清取样,Elisa(酶联免疫吸附)法测定各组小鼠血清IL-2水平,用酶标仪在450nnm波长下测量各小鼠血清的OD(吸光度)值并用应用labsys雷勃酶标仪软件v5.01计算出各孔的IL-2浓度；剥取荷瘤小鼠皮下移植瘤标本,电子天平称重并做好记录,以计算各组荷瘤小鼠抑瘤率。然后取样,用10%福尔马林固定,标本用免疫组织化学染色后,在倒置显微镜下检测各组小鼠皮下移植瘤内CD25+细胞,早期凋亡肿瘤细胞Cleaved-caspase3表达情况；摘取各组小鼠胸腺、脾脏,电子天平称重后,做好记录,以计算各种小鼠胸腺指数及脾指数。
结果：
1.人参皂苷Rh2灌胃组与酒精灌胃对照组相比,其抑瘤率为81.76%,5-FU腹腔注射治疗组与酒精灌胃对照组相比,其抑瘤率为91.32%。
2.人参皂苷Rh2对荷结肠癌小鼠皮下移植瘤内的早期凋亡肿瘤细胞表达Cleaved-caspase3的影响：人参皂苷Rh2灌胃组与酒精灌胃对照组相比,小鼠皮下移植瘤内的早期凋亡肿瘤细胞Cleaved-caspase3表达率明显增加(P<0.01),具有显著统计学意义。
3.人参皂苷Rh2(0.4%乙醇混悬液)灌胃治疗组与5-FU腹腔注射治疗组相比,小鼠皮下移植瘤内的早期凋亡肿瘤细胞Cleaved-caspase3表达率不及后者(P<0.01)。
4.5-FU腹腔注射治疗组同人参皂苷Rh2灌胃组、酒精灌胃对照组相比胸腺指数、脾脏指数、血清IL-2水平均明显降低(P<0.05)。
5.人参皂苷Rh2对荷结肠癌小鼠的免疫器官的影响：在该实验中人参皂苷Rh2灌胃组与酒精灌胃对照组相比,小鼠的胸腺指数、脾脏指数差异无统计学意义(P>0.05)。
6.人参皂苷Rh2对荷结肠癌小鼠的细胞因子的影响：人参皂苷Rh2灌胃组与酒精灌胃对照组相比,小鼠的血清IL-2水平差异无统计学意义(P>0.05)。
7.人参皂苷Rh2对荷结肠癌小鼠皮下移植瘤内的CD25+细胞的影响：人参皂苷Rh2灌胃组与酒精灌胃对照组相比,小鼠皮下移植瘤内的CD25+细胞浸润无明显增多(P>0.05)。
8.小鼠荷瘤以后,胸腺指数、脾脏指数、血清IL-2水平均较正常小鼠降低(P<0.05),与前人动物实验结果一致。
结论：人参皂苷Rh2 0.4mg/kg(0.4%乙醇混悬液)经口服能够显著抑制小鼠结肠癌CT-26肿瘤细胞生长,增加小鼠皮下移植瘤内的早期凋亡肿瘤细胞Cleaved-caspase3阳性表达率,促进小鼠结肠癌CT-26肿瘤细胞凋亡,但作用不及5-FU。从毒副作用方面来说,人参皂苷Rh2 0.4mg/kg经口服在发挥抗肿瘤作用的同时没有抑制荷瘤小鼠免疫功能。但对提高荷小鼠结肠癌CT-26小鼠胸腺指数、脾指数血清IL-2水平,肿瘤局部CD25+细胞阳性表达率也无明显作用。
Objective:To research effects of ginsenosideRh2 on tumor and immune index of colon cancer CT26 mice, searching for active ingredients of Chinese medicine which shows strong anti-tumor effect but less side effects.
Methods:First of all, tumor cell lines were cultured and passaged. When the tumor cells reached a certain number, they were digested and off the sidewall with trypsin, later the tumor cells suspension were made by physiological saline, the tumor cells suspension was prepared。The tumor cells suspension was inoculated subcutaneously in 32 healthy BALB/c mice on the right neck and back. The mice were equal number of male and female. Two weeks after the inoculation, the tumor models were made and they were stable.24 of the mice of which the transplanted tumors subcutaneously were nearly the same size were randomly divided into three groups:ethanol ig group, ginsenosideRh2 ig group and 5-FU ip group.21 days after treatment, they were weighed and the data were recorded. Remove eyes of the mice, blood samples were gathered, centrifuged after standing, draw the upper Serum samples, Detect levels of serum IL-2 with Enzyme-linked immunosorbent assay. OD (absorbance) value of every serum IL-2 was measured at 450nm wavelength with Elisa Reader. Applied labsys Elisa Reader software v5.01 calculate every concentration of IL-2. Stripped mice subcutaneous tumor specimens, weighed by electronic balance and the data were recorded, preparing for calculating the inhibition rate of every group. And then sampled, fixed in 10% formalin, specimens were treated with immunohistochemical staining, detect the CD25+cell,Cleaved-caspase3 expression in the subcutaneous tumor in mice with inverted microscope. Removed the thymus, spleen of every mice, weighed and the data were recorded, after then calculated thymus index, spleen index.
Results:1. Compared with ethanol ig group, the inhibition rate of ginsenosideRh2 ig group is 81.76%. Compared with ethanol ig group, the inhibition rate of 5-FU ip group is 90.32%.
2. The effect of ginsenosideRh2 on Cleaved-caspase3 expression in the subcutaneous tumor in mice:Compared with ethanol ig group, the Cleaved-caspase3 expression rate in the subcutaneous tumor of ginsenosideRh2 ig group Significantly increased, shows statistically significance.
3 Compared with 5-FU ip group, the CD25+ cell expression rate in the subcutaneous tumor of ginsenosideRh2 ig group is less than the former.
4. Compared with ginsenosideRh2 ig group and ethanol ig group, the levels of serum IL-2, thymus index and spleen index of the 5-FU ip group decreased.
5. The effect of ginsenosideRh2 on immune organs of tumor bearing mice: Compared with ethanol ig group, thymus index and spleen index of the ginsenosideRh2 ig group shows no statistically significance.
6. The effect of ginsenosideRh2 on Cytokines of tumor bearing mice:Compared with ethanol ig group, the levels of serum IL-2 of ginsenosideRh2 ig group shows no statistically significance.
7. The effect of ginsenosideRh2 on CD25+ cell expression rate in the subcutaneous tumor in mice:Compared with ethanol ig group, the CD25+ cell expression rate in the subcutaneous tumor of ginsenosideRh2 ig group shows no statistically significance.
8. Compared with the intact mice, the levels of serum IL-2, the thymus index and spleen index of mice decreased after bearing tumor.
Conclusion:GinsenosideRh2 can inhibit the growth of colon CT26 tumor through ig 0.4mg/kg. Increase the Cleaved-caspase3 expression rate in the subcutaneous tumor. Promote the apoptosis of colon CT26 tumor. But it is no better than 5-FU. But in terms of side effects, it is better than 5-FU.And no Significant effect on increasing the levels of serum IL-2, the thymus index and spleen index of the mice bearing tumor.
方法：首先进行肿瘤细胞系的培养传代。肿瘤细胞培养至一定数量时,用胰蛋白酶消化重悬,制备成肿瘤细胞悬液,接种于32只健康雌雄各半BALB/c小鼠右侧颈背部皮下,建立荷小鼠结肠癌CT-26动物模型。2周后动物肿瘤模型已稳定,除正常对照组外,将成瘤均匀且肿瘤大小相近的24只荷瘤小鼠模型随机分成3组：0.4%乙醇灌胃对照组、人参皂苷Rh2(0.4%乙醇混悬液)灌胃治疗组、5-FU腹腔注射治疗组。治疗21天后,各组小鼠称重,摘取小鼠眼球,收集血液标本,静置离心后吸取上层血清取样,Elisa(酶联免疫吸附)法测定各组小鼠血清IL-2水平,用酶标仪在450nnm波长下测量各小鼠血清的OD(吸光度)值并用应用labsys雷勃酶标仪软件v5.01计算出各孔的IL-2浓度；剥取荷瘤小鼠皮下移植瘤标本,电子天平称重并做好记录,以计算各组荷瘤小鼠抑瘤率。然后取样,用10%福尔马林固定,标本用免疫组织化学染色后,在倒置显微镜下检测各组小鼠皮下移植瘤内CD25+细胞,早期凋亡肿瘤细胞Cleaved-caspase3表达情况；摘取各组小鼠胸腺、脾脏,电子天平称重后,做好记录,以计算各种小鼠胸腺指数及脾指数。
结果：
1.人参皂苷Rh2灌胃组与酒精灌胃对照组相比,其抑瘤率为81.76%,5-FU腹腔注射治疗组与酒精灌胃对照组相比,其抑瘤率为91.32%。
2.人参皂苷Rh2对荷结肠癌小鼠皮下移植瘤内的早期凋亡肿瘤细胞表达Cleaved-caspase3的影响：人参皂苷Rh2灌胃组与酒精灌胃对照组相比,小鼠皮下移植瘤内的早期凋亡肿瘤细胞Cleaved-caspase3表达率明显增加(P<0.01),具有显著统计学意义。
3.人参皂苷Rh2(0.4%乙醇混悬液)灌胃治疗组与5-FU腹腔注射治疗组相比,小鼠皮下移植瘤内的早期凋亡肿瘤细胞Cleaved-caspase3表达率不及后者(P<0.01)。
4.5-FU腹腔注射治疗组同人参皂苷Rh2灌胃组、酒精灌胃对照组相比胸腺指数、脾脏指数、血清IL-2水平均明显降低(P<0.05)。
5.人参皂苷Rh2对荷结肠癌小鼠的免疫器官的影响：在该实验中人参皂苷Rh2灌胃组与酒精灌胃对照组相比,小鼠的胸腺指数、脾脏指数差异无统计学意义(P>0.05)。
6.人参皂苷Rh2对荷结肠癌小鼠的细胞因子的影响：人参皂苷Rh2灌胃组与酒精灌胃对照组相比,小鼠的血清IL-2水平差异无统计学意义(P>0.05)。
7.人参皂苷Rh2对荷结肠癌小鼠皮下移植瘤内的CD25+细胞的影响：人参皂苷Rh2灌胃组与酒精灌胃对照组相比,小鼠皮下移植瘤内的CD25+细胞浸润无明显增多(P>0.05)。
8.小鼠荷瘤以后,胸腺指数、脾脏指数、血清IL-2水平均较正常小鼠降低(P<0.05),与前人动物实验结果一致。
结论：人参皂苷Rh2 0.4mg/kg(0.4%乙醇混悬液)经口服能够显著抑制小鼠结肠癌CT-26肿瘤细胞生长,增加小鼠皮下移植瘤内的早期凋亡肿瘤细胞Cleaved-caspase3阳性表达率,促进小鼠结肠癌CT-26肿瘤细胞凋亡,但作用不及5-FU。从毒副作用方面来说,人参皂苷Rh2 0.4mg/kg经口服在发挥抗肿瘤作用的同时没有抑制荷瘤小鼠免疫功能。但对提高荷小鼠结肠癌CT-26小鼠胸腺指数、脾指数血清IL-2水平,肿瘤局部CD25+细胞阳性表达率也无明显作用。
Objective:To research effects of ginsenosideRh2 on tumor and immune index of colon cancer CT26 mice, searching for active ingredients of Chinese medicine which shows strong anti-tumor effect but less side effects.
Methods:First of all, tumor cell lines were cultured and passaged. When the tumor cells reached a certain number, they were digested and off the sidewall with trypsin, later the tumor cells suspension were made by physiological saline, the tumor cells suspension was prepared。The tumor cells suspension was inoculated subcutaneously in 32 healthy BALB/c mice on the right neck and back. The mice were equal number of male and female. Two weeks after the inoculation, the tumor models were made and they were stable.24 of the mice of which the transplanted tumors subcutaneously were nearly the same size were randomly divided into three groups:ethanol ig group, ginsenosideRh2 ig group and 5-FU ip group.21 days after treatment, they were weighed and the data were recorded. Remove eyes of the mice, blood samples were gathered, centrifuged after standing, draw the upper Serum samples, Detect levels of serum IL-2 with Enzyme-linked immunosorbent assay. OD (absorbance) value of every serum IL-2 was measured at 450nm wavelength with Elisa Reader. Applied labsys Elisa Reader software v5.01 calculate every concentration of IL-2. Stripped mice subcutaneous tumor specimens, weighed by electronic balance and the data were recorded, preparing for calculating the inhibition rate of every group. And then sampled, fixed in 10% formalin, specimens were treated with immunohistochemical staining, detect the CD25+cell,Cleaved-caspase3 expression in the subcutaneous tumor in mice with inverted microscope. Removed the thymus, spleen of every mice, weighed and the data were recorded, after then calculated thymus index, spleen index.
Results:1. Compared with ethanol ig group, the inhibition rate of ginsenosideRh2 ig group is 81.76%. Compared with ethanol ig group, the inhibition rate of 5-FU ip group is 90.32%.
2. The effect of ginsenosideRh2 on Cleaved-caspase3 expression in the subcutaneous tumor in mice:Compared with ethanol ig group, the Cleaved-caspase3 expression rate in the subcutaneous tumor of ginsenosideRh2 ig group Significantly increased, shows statistically significance.
3 Compared with 5-FU ip group, the CD25+ cell expression rate in the subcutaneous tumor of ginsenosideRh2 ig group is less than the former.
4. Compared with ginsenosideRh2 ig group and ethanol ig group, the levels of serum IL-2, thymus index and spleen index of the 5-FU ip group decreased.
5. The effect of ginsenosideRh2 on immune organs of tumor bearing mice: Compared with ethanol ig group, thymus index and spleen index of the ginsenosideRh2 ig group shows no statistically significance.
6. The effect of ginsenosideRh2 on Cytokines of tumor bearing mice:Compared with ethanol ig group, the levels of serum IL-2 of ginsenosideRh2 ig group shows no statistically significance.
7. The effect of ginsenosideRh2 on CD25+ cell expression rate in the subcutaneous tumor in mice:Compared with ethanol ig group, the CD25+ cell expression rate in the subcutaneous tumor of ginsenosideRh2 ig group shows no statistically significance.
8. Compared with the intact mice, the levels of serum IL-2, the thymus index and spleen index of mice decreased after bearing tumor.
Conclusion:GinsenosideRh2 can inhibit the growth of colon CT26 tumor through ig 0.4mg/kg. Increase the Cleaved-caspase3 expression rate in the subcutaneous tumor. Promote the apoptosis of colon CT26 tumor. But it is no better than 5-FU. But in terms of side effects, it is better than 5-FU.And no Significant effect on increasing the levels of serum IL-2, the thymus index and spleen index of the mice bearing tumor.
引文
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