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纸质出版日期:2018
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尹丽颖, 肖洪彬, 敖鹏, 等. 辽东楤木叶总皂苷对荷结肠癌细胞裸鼠移植瘤TLR-4/NF-B信号通路及炎性因子的影响[J]. 中国实验方剂学杂志, 2018,24(24):152-157.
YIN Li-ying, XIAO Hong-bin, AO Peng, et al. Effect of Total Saponins in Leaves on TLR-4/NF-B Signal Pathway and Inflammatory Factors in Xenografts from Nude Mice Bearing Human Colon Cancer Cells[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(24): 152-157.
尹丽颖, 肖洪彬, 敖鹏, 等. 辽东楤木叶总皂苷对荷结肠癌细胞裸鼠移植瘤TLR-4/NF-B信号通路及炎性因子的影响[J]. 中国实验方剂学杂志, 2018,24(24):152-157. DOI: 10.13422/j.cnki.syfjx.20182125.
YIN Li-ying, XIAO Hong-bin, AO Peng, et al. Effect of Total Saponins in Leaves on TLR-4/NF-B Signal Pathway and Inflammatory Factors in Xenografts from Nude Mice Bearing Human Colon Cancer Cells[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(24): 152-157. DOI: 10.13422/j.cnki.syfjx.20182125.
目的:观察辽东楤木叶总皂苷(ETS)对荷瘤裸鼠人结肠癌HT-29移植瘤Toll样受体-4/核转录因子-κB(TLR-4/NF-κB)信号通路及血清中炎性因子的影响,从而探讨其抑瘤机制。方法:将人结肠癌HT-29细胞株接种于50只裸鼠的右腋部皮下,建立人结肠癌异位皮下移植瘤的动物模型。将接种后的裸鼠随机分为5组,每组10只,即模型组,ETS低、中、高剂量组(37.5,75,150 mg·kg-1),5-氟尿嘧啶组(20 mg·kg-1)。分组后2 d进行给药,5-氟尿嘧啶组腹腔注射给药,隔日1次;ETS低、中、高组给药;模型组给灌胃等体积的生理盐水;连续给药8周。眼眶取血,酶联免疫吸附法(ELISA)检测肿瘤坏死因子-α(TNF-α),白细胞介素-1(IL-1);实时荧光定量聚合酶链式反应(Real-time PCR)检测肿瘤组织中TLR-4,NF-κB mRNA表达水平;光学显微镜和透射电子显微镜下观察ETS对荷瘤裸鼠人结肠癌HT-29移植瘤形态学方面的影响。结果:病理组织学和超微病理学实验显示各给药组肿瘤组织均有不同程度的损伤,与模型组比较,ETS低、中、高剂量组及5-氟脲嘧啶组对荷瘤裸鼠人结肠癌移植瘤均有不同程度的抑制作用(P<0.05,P<0.01),4组抑瘤率分别是20.14%,32.43%,59.56%,63.58%;与模型组比较,ETS各剂量组TLR-4,NF-κB mRNA及TNF-α,IL-1水平表达明显降低(P<0.05)。结论: ETS可有效抑制结肠癌肿瘤的生长,其机制可能与调控TLR-4/NF-κB信号通路,减少炎性因子表达有关。
Objective: To observe the effect of total saponins in Aralia elata leaves (ETS) Toll-like receptor-4/nuclear factor-κB(TLR-4/NF-κB) signal pathway and inflammatory factors in xenografts from nude mice bearing human colon cancer cells
so as to explore the tumor suppression mechanism. Method: Human colon cancer HT-29 cell line was inoculated in the right armpit of 50 nude mice
so as to es tablelish an animal model of ectopic subcutaneous tumor of human colon cancer. Then the mice were randomly divided into 5 groups
with 10 in each group:model group
low-dose group (37.5 mg·kg-1)
medium-dose group (75 mg·kg-1)
high-dose group (150 mg·kg-1)
and positive control group (5-FU 20 mg·kg-1). Two days after grouping
the mice in positive control group were given ip once every two days; ETS was given to low
medium and high-dose groups
ig; model group was given equal volume of normal saline. The administration lasted for 8 weeks. Enzyme linked immunosorbent assay (ELISA)was used to detect tumor necrosis factor-α(TNF-α)
interleukin 1(IL-1); Real-time polymerase chain reaction(Real-time PCR) was used to detect the expression levels of gene of TLR-4 and NF-κB in tumor tissue. The effect of ETS on the morphology of HT-29 transplanted tumor of human colon cancer in nude mice were observed under optical and transmission electron microscopy. Result: Compared with model group
low
middle and high-dose ETS groups and positive control groups had different inhibitory effects on human colon cancer transplanted tumor in nude mice(P<0.01). The tumor suppressor rates were 20.14%
32.43%
59.56% and 63.58%
respectively. TLR-4
NF-κB significantly decreased the mRNA expressions of drug serum inflammatory factor and tumor tissues(P<0.05). Histopathology and ultramicro pathological experiments showed that the tumor tissue in each group had varying degrees of damage. Conclusion: ETS can inhibit the proliferation of tumor
and the mechanism may be associated with regulating TLR-4/NF-κB pathway and reducing inflammatory factors.
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