大蒜素促进子宫内膜癌荷瘤小鼠肿瘤细胞凋亡
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摘要
目的探讨大蒜素对子宫内膜癌荷瘤小鼠肿瘤组织的影响及其机制。方法取40只BALB/c裸鼠和人子宫内膜癌细胞系Ishikawa建立子宫内膜癌荷瘤小鼠模型。实验分为模型组(model)和腹腔注入大蒜素(allicin)10、20和40 mg/kg每组2 mL为干预组。测量瘤体积、计算抑瘤率、HE观察病理变化及流式细胞计量术检测细胞凋亡率;实时荧光定量聚合酶链反应(RT-qPCR)检测TLR4和MyD88 mRNA表达;Western blot检测TLR4和MyD88蛋白表达。结果各干预组瘤体积缩小,呈剂量依赖性增加抑瘤率(P<0.05);干预组细胞皱缩、核染色质向边缘集中、片状坏死等病理表现,肿瘤组织细胞凋亡率明显降低(P<0.05);肿瘤组织TLR4、MyD88 mRNA及蛋白相对表达量降低(P<0.05)。结论大蒜素可抑制子宫内膜癌荷瘤小鼠肿瘤增长及促进细胞凋亡。
Objective To investigate the effect of allicin on endometrial cancer-bearing mice and its mechanism. Methods Forty BALB/c nude mice and human endometrial carcinoma cell line Ishikawa were used to establish endometrial carcinoma bearing mice model. The experiment was divided into model group(M group) and allicin group A(low dose), B(medium dose) and C(high dose). Allicin groups were given intraperitoneal injection of 10, 20 and 40 mg/kg of allicin dissolved in 2 mL sterile saline respectively. Group M was given 2 mL sterile saline intraperitoneal injection once every other day for 4 weeks. Tumor volume, inhibition rate, pathological changes and apoptotic rate of tumor tissue before and after intervention were compared; TLR4 and MyD88 were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR); TLR4 and MyD88 were detected by Western blot. Results After intervention, there were significant differences in the volume of tumors between each group and every two groups(P<0.05). The inhibition rate of tumors in group C was the highest, followed by that in group B, and the lowest in group A, with significant differences between each two groups(P<0.05). There was no abnormalities in the histological structure of tumors in group M. The pathological manifestations of tumors in group A, B and C included cell shrinkage, centralization of nuclear chromatin to the margin and patchy necrosis. The apoptoticrate of tissues was significantly decreased, and the relative expression of TLR4, MyD88 and protein in tumor tissues was decreased. Conclusions Allicin can inhibit the growth of endometrial cancer-bearing mice and promote cell apoptosis.
Objective To investigate the effect of allicin on endometrial cancer-bearing mice and its mechanism. Methods Forty BALB/c nude mice and human endometrial carcinoma cell line Ishikawa were used to establish endometrial carcinoma bearing mice model. The experiment was divided into model group(M group) and allicin group A(low dose), B(medium dose) and C(high dose). Allicin groups were given intraperitoneal injection of 10, 20 and 40 mg/kg of allicin dissolved in 2 mL sterile saline respectively. Group M was given 2 mL sterile saline intraperitoneal injection once every other day for 4 weeks. Tumor volume, inhibition rate, pathological changes and apoptotic rate of tumor tissue before and after intervention were compared; TLR4 and MyD88 were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR); TLR4 and MyD88 were detected by Western blot. Results After intervention, there were significant differences in the volume of tumors between each group and every two groups(P<0.05). The inhibition rate of tumors in group C was the highest, followed by that in group B, and the lowest in group A, with significant differences between each two groups(P<0.05). There was no abnormalities in the histological structure of tumors in group M. The pathological manifestations of tumors in group A, B and C included cell shrinkage, centralization of nuclear chromatin to the margin and patchy necrosis. The apoptoticrate of tissues was significantly decreased, and the relative expression of TLR4, MyD88 and protein in tumor tissues was decreased. Conclusions Allicin can inhibit the growth of endometrial cancer-bearing mice and promote cell apoptosis.
引文
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[2] Zou X,Liang J,Sun J,et al.Allicin sensitizes hepatocellular cancer cells to anti-tumor activity of 5-fluorouracil through ROS-mediated mitochondrial pathway[J].J Pharmacol Sci,2016,131:233-240.
[3] 胡晓艳,姜梁.大蒜素对子宫颈癌Hela细胞增殖的影响[J].中国妇幼保健,2012,27:731-732.
[4] 贾丽.大蒜素对荷子宫内膜癌裸小鼠移植瘤生长的影响及其机制研究[J].医学研究杂志,2017,46:120-123.
[5] Chung JW,Noh EJ,Zhao HL,et al.Anti-inflammatory activity of prosapogenin methyl ester of platycodin D via nuclear factor-kappaB pathway inhibition[J].Biol Pharm Bull,2008,31:2114-2120.
[6] Yegin Akcay GF,Tas EE,Yavuz AF.Is postmenopausal endometrial fluid collection alone a risk factor for endometrial cancer?[J].Pak J Med Sci,2018,34:54-57.
[7] Panyod S,Wu WK,Ho CT,et al.Diet supplementation with allicin protects against alcoholic fatty liver disease in mice by improving anti-inflammation and antioxidative functions[J].J Agric Food Chem,2016,64:7104-7113.
[8] 张彬,陈丽红,陈秀慧,等.大蒜素促进人子宫内膜癌细胞株(RL-952)细胞凋亡的机制[J].中国老年学杂志,2016,36:285-287.
[9] Luo R,Fang D,Hang H,et al.The mechanism in gastric cancer chemoprevention by Allicin[J].Anticancer Agents Med Chem,2016,16:802-809.
[10] Hosseini H,Li Y,Kanellakis P,et al.Toll-like receptor (TLR)4 and MyD88 are essential for atheroprotection by peritoneal B1a B cells[J].J Am Heart Assoc,2016,5:186-188.
[11] Guo J,Liang W,Li J,et al.Knockdown of FSTL1 inhibits oxLDL-induced inflammation responses through the TLR4/MyD88/NF-κB and MAPK pathway[J].Biochem Biophys Res Commun,2016,478:1528-1533.
[12] 王畅.白术内酯Ⅰ靶向MD2抑制TLR4/MyD88/AKT通路增加紫杉醇诱导的卵巢癌细胞凋亡[D].广西医科大学,2014:21-24.