双氢青蒿素对人卵巢癌裸鼠移植瘤的作用及P53表达的影响

发布时间：2018-03-26 05:22

本文选题：双氢青蒿素　切入点：裸鼠移植瘤　出处：《山西医科大学》2014年硕士论文

【摘要】：目的:研究双氢青蒿素（DHA）对人卵巢癌细胞株H0-8910裸鼠皮下移植瘤的作用及P53表达，探讨其可能的作用机制。方法: H0-8910注入裸小鼠腋下，建立人卵巢癌裸鼠移植瘤的模型,将造模成功的30只裸鼠随机分为5组，即空白组(生理盐水)、低剂量DHA组(100mg/kg)、中剂量DHA组(150mg/kg)、高剂量DHA组(200mg/kg)，顺铂对照组(2mg/kg)，6只/组。顺铂采取腹腔注射的方式，，给药5d后停药，其余组均采用灌胃的方式连续给药10d，第11d处死裸鼠，称取各组移植瘤重量,比较各组用药后移植瘤的抑瘤率；免疫组织化学法和western-blot法检测肿瘤组织内P53蛋白的表达；实时荧光定量PCR法来测定肿瘤组织内P53基因的表达。结果:①DHA有一定的抑制裸鼠移植瘤生长的作用，且有浓度依赖性。低、中、高剂量DHA组及顺铂组的抑瘤率分别为24.8%、37.2％、55.4%及56.2%,各组和空白组比较，差异均有统计学意义，P 0.05,低、中剂量组与顺铂组抑瘤率比较差异有统计学意义, P 0.05，高剂量组与顺铂组抑瘤率比较差异无统计学意义。②病理学镜下见细胞体积大，胞质较疏松，核深染，核固缩、核碎裂及核溶解的程度不同，细胞中能看到局灶性坏死。③免疫组化法结果证实随着DHA剂量的增加突变型P53蛋白表达减弱；western-blot法检测到DHA组野生型P53蛋白的表达上调。④实时荧光定量PCR法检测到DHA组野生型P53基因的表达上调。结论: DHA可以明显的抑制人卵巢癌裸鼠移植瘤的生长，且有浓度依赖性，其作用机制可能与上调野生型P53的表达导致细胞凋亡相关。
[Abstract]:Aim: to study the effect of dihydroartemisinin (DHA) on subcutaneous transplantation of human ovarian cancer cell line H0-8910 and the expression of p53 in nude mice. Methods: H0-8910 was injected into the axillary of nude mice to establish the transplanted tumor model of human ovarian cancer in nude mice. Thirty nude mice were randomly divided into 5 groups. That is, the blank group (normal saline, low dose DHA group, low dose DHA group), middle dose DHA group (150 mg / kg), high dose DHA group (200 mg / kg), cisplatin control group (2 mg / kg), 6 rats / group. Cisplatin was injected intraperitoneally and stopped after 5 days of administration. All the other groups were administrated by gavage for 10 days, the nude mice were killed on the 11th day, the tumor weight of each group was taken out, the tumor inhibition rate was compared, the expression of p53 protein in tumor tissue was detected by immunohistochemical method and western-blot method. The expression of p53 gene in tumor tissues was detected by real-time fluorescence quantitative PCR. Results the growth of transplanted tumor in nude mice was inhibited by 1: 1DHA in a concentration-dependent manner. The inhibitory rates of low, middle and high dose DHA and cisplatin groups were 55.4% and 56.2%, respectively. There was significant difference between the two groups (P 0.05, P 0.05, P < 0.05). There was significant difference in tumor inhibition rate between middle dose group and cisplatin group (P 0.05). There was no significant difference in tumor inhibition rate between high dose group and cisplatin group. 2 there was no significant difference in tumor inhibition rate between high dose group and cisplatin group. 2. Under pathological microscope, large cell size, loose cytoplasm, deep staining of nucleus and pyknosis of nucleus were found. The degree of nuclear fragmentation and dissolution varies, The expression of p53 protein decreased with the increase of DHA dose. The expression of wild-type p53 protein was up-regulated by Western blot in DHA group. 4 real-time fluorescence quantitative PCR method was used to detect DHA. The expression of wild type p53 gene was up-regulated. Conclusion: DHA can inhibit the growth of human ovarian cancer xenografts in a dose-dependent manner, and its mechanism may be related to the up-regulation of wild-type p53 expression and apoptosis.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.31

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