[1]季 滢,郑艳莉,韩 云,等.尼美舒利对宫颈癌荷瘤裸鼠移植瘤的影响及机制实验研究[J].陕西医学杂志,2024,(8):1026-1030.[doi:DOI:10.3969/j.issn.1000-7377.2024.08.004]
　JI Ying,ZHENG Yanli,HAN Yun,et al.Effect of nimesulide on cervical cancer tumor-bearing nude mice xenograft and its mechanism[J].,2024,(8):1026-1030.[doi:DOI:10.3969/j.issn.1000-7377.2024.08.004]
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尼美舒利对宫颈癌荷瘤裸鼠移植瘤的影响及机制实验研究
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
期数:
2024年8期
页码:
1026-1030
栏目:
基础研究
出版日期:
2024-08-05

文章信息/Info

Title:
Effect of nimesulide on cervical cancer tumor-bearing nude mice xenograft and its mechanism
作者:
季 滢1; 郑艳莉1; 韩 云2; 孙蓉蓉1; 朱 奕1
(1.南通大学第二附属医院妇产科,江苏 南通 226000; 2.上海市肿瘤研究所,上海 200032)
Author(s):
JI Ying; ZHENG Yanli; HAN Yun; SUN Rongrong; ZHU Yi
(Department of Obstetrics and Gynecology,the Second Affiliated Hospital of Nantong University,Nantong 226000,China)
关键词:
宫颈癌;  移植瘤;  尼美舒利;  过氧化物酶体增殖物激活受体γ;  第10号染色体缺失的磷酸酶及张力蛋白同源的基因;  蛋白激酶B;  裸鼠
Keywords:
Cervical cancer;  Xenograft;  Nimesulide;  Peroxisome proliferator-activated receptor γ;  Phosphatase and tensin homolog deleted on chromosome ten;  Protein kinase B;  Nude mice
分类号:
R -33
DOI:
DOI:10.3969/j.issn.1000-7377.2024.08.004
文献标志码:
A
摘要:
目的:探讨尼美舒利对宫颈癌荷瘤裸鼠移植瘤的影响及可能的机制。方法:建立人宫颈癌C33A细胞裸鼠皮下移植瘤模型40只,随机分为模型组、尼美舒利组、过氧化物酶体增殖物激活受体γ(PPARγ)抑制剂组、联合组,每组10只。尼美舒利组每天给予20 mg/kg尼美舒利灌胃,模型组给予等量0.5%羟甲基纤维素钠灌胃,PPARγ抑制剂组每天给予10 mg/kg PPARγ抑制剂GW9662灌胃,联合组给予尼美舒利联合PPARγ抑制剂处理,均连续干预4周。采用流式细胞术检测各组裸鼠脾脏自然杀伤(NK)细胞活性。采用TUNEL法检测各组裸鼠移植瘤细胞凋亡情况。采用Western blot检测移植瘤组织PPARγ、第10号染色体缺失的磷酸酶及张力蛋白同源的基因(PTEN)、蛋白激酶B(AKT)、p-AKT蛋白表达。结果:40只裸鼠皮下出现直径至少5 mm的肿瘤结节,且未出现红肿或坏死的迹象,模型建立成功。与模型组比较,尼美舒利组NK细胞活性增强,PPARγ抑制剂组NK细胞活性降低(均P<0.05)。与尼美舒利组比较,联合组NK细胞活性降低(P<0.05)。与PPARγ抑制剂组比较,联合组NK细胞活性增强(P<0.05)。各组干预后第3、6、9、12天,与模型组比较,尼美舒利组移植瘤体积缩小,PPARγ抑制剂组移植瘤体积增大(均P<0.05); 与尼美舒利组比较,联合组移植瘤体积增大(P<0.05); 与PPARγ抑制剂组比较,联合组移植瘤体积缩小(P<0.05)。与模型组比较,尼美舒利组移植瘤细胞凋亡率及PPARγ、PTEN蛋白表达量升高,p-AKT/AKT比值降低; PPARγ抑制剂组移植瘤细胞凋亡率及PPARγ、PTEN蛋白表达量降低,p-AKT/AKT比值升高(均P<0.05)。与尼美舒利组比较,联合组移植瘤细胞凋亡率及PPARγ、PTEN蛋白表达量降低,p-AKT/AKT比值升高(均P<0.05)。与PPARγ抑制剂组比较,联合组移植瘤细胞凋亡率及PPARγ蛋白、PTEN蛋白表达量升高,p-AKT/AKT比值降低(均P<0.05)。结论:尼美舒利可抑制宫颈癌荷瘤裸鼠移植瘤生长,增强NK细胞活性,促进肿瘤细胞凋亡,其作用机制可能与上调PPARγ及PTEN/AKT通路有关。
Abstract:
Objective:To investigate the effect of nimesulide on cervical cancer tumor-bearing nude mice xenograft and its possible mechanism.Methods:A total of 40 human cervical carcinoma C33A cell subcutaneous transplantation tumor models in nude mice were established and randomly divided into model group,nimesulide group,peroxisome proliferator-activated receptor γ(PPARγ)inhibitor group and combined group,with 10 in each group.Nimesulide group was given 20 mg/kg of nimesulide daily,the model group was given 0.5% sodium methylol cellulose orally,the PPARγ inhibitor group was given 10 mg/kg PPARγ inhibitor GW9662 orally,and the combination group was given imesulide combined with PPARγ inhibitor treatment,all of which were continuously interfered with for four weeks.The spleen natural killer(NK)cells were detected by flow cytometry in each group.The apoptosis of transplanted tumor cells in each group was detected by TUNEL method.The expression of PPARγ,phosphatase and tensin homolog deleted on chromosome ten(PTEN),protein kinase B(AKT),and p-AKT proteins were detected by Western blot.Results:Subcutaneous nodules with a diameter of at least 5 mm were found in forty nude mice without signs of redness,swelling or necrosis.The model was established successfully.Compared with model group,NK cell activity was enhanced in nimesulide group and decreased in PPARγ inhibitor group(all P<0.05).Compared with nimesulide group,NK cell activity in combination group was decreased(all P<0.05).Compared with PPARγ inhibitor group,NK cell activity in combination group was enhanced(P<0.05).On days 3,6,9 and 12 after intervention,tumor volume decreased in nimesulide group and increased in PPARγ inhibitor group compared with model group(all P<0.05).Compared with nimesulide group,the graft volume in combination group was increased(P<0.05).Compared with the PPARγ inhibitor group,the graft volume of the combined group decreased(P<0.05).Compared with model group,the apoptosis rate and the expression levels of PPARγ and PTEN protein in nimesulide group were increased,the p-AKT/AKT ratio was decreased,and the apoptosis rate and the expression levels of PPARγ and PTEN protein in PPARγ inhibitor group were decreased,the p-AKT/AKT ratio was increased(all P<0.05).Compared with nimesulide group,apoptosis rate,the expression levels of PPARγ and PTEN protein were decreased in combination group,and p-AKT/AKT ratio was increased(all P<0.05).Compared with PPARγ inhibitor group,apoptosis rate,PPARγ protein and PTEN protein expression in combination group were increased and p-AKT/AKT ratio was decreased(all P<0.05).Conclusion:Nimesulide can inhibit the growth of xenograft in cervical cancer tumor-bearing nude mice,enhance the activity of NK cells and promote the apoptosis of tumor cells,and its mechanism may be related to the up-regulation of PPARγ and PTEN/AKT pathway.

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备注/Memo

备注/Memo:
基金项目:癌基因与相关基因国家重点实验室科研项目(KF2201); 江苏省南通市卫生健康委员会科研课题(MA2021015)
更新日期/Last Update: 2024-08-08