阻断TLR4信号通路对结肠癌细胞CT26裸鼠种植瘤生长和凋亡的影响  

Effect of blocking TLR4 signaling pathway on the growth and apoptosis of tumors of colorectal cancer cell line CT26 implanted in nude mice

作　　者：何卉欣 蒋梦萍[1] 刘慧玲[1] 江洁[1] 尉秀清[1] 

机构地区：[1]中山大学附属第三医院消化内科,广州510630

出　　处：《新医学》2015年第4期216-220,共5页Journal of New Medicine

基　　金：国家自然基金面上项目(81470848;81272640)

摘　　要：目的研究阻断Toll样受体4(TLR4)信号通路对小鼠结肠癌细胞CT26裸鼠种植瘤生长和凋亡的影响。方法建立结肠癌细胞CT26裸鼠种植瘤模型,12只鼠成瘤后随机分成实验组及对照组,分别腹腔内注射TLR4信号通路阻断剂CLI-095(3 mg/kg)和相同公斤体积的二甲基亚砜(DMSO),并测定种植瘤的生长曲线;种植瘤石蜡包埋切片作苏木素-伊红染色观察病理组织学改变,TUNEL法检测瘤组织凋亡情况,蛋白免疫印迹法检测TLR4、cleaved caspase-3等蛋白表达。结果在实验结束时,实验组瘤体体积为(2.39±0.32)cm3,对照组瘤体体积为(1.77±0.25)cm3,实验组瘤体显著大于对照组(t=3.817,P=0.004)。实验组肿瘤细胞排列较致密,仅有局部坏死;对照组肿瘤细胞密度较低、排列散乱,坏死显著。实验组癌组织凋亡指数为(9.86±2.80)%,明显低于对照组的(22.57±4.93)%,t=-7.091,P<0.001。2组癌组织TLR4蛋白的表达无显著差异,实验组cleaved caspase-3蛋白的表达显著低于对照组。结论阻断TLR4信号通路,可以抑制结肠癌细胞株CT26种植瘤细胞的凋亡,从而有利于肿瘤生长。Objective To investigate the effect of blocking TLR4 signaling pathway on the growth and apoptosis of the tumors of colorectal cancer cell line CT26 implanted in nude mice.Methods Twelve nude mouse models implanted with colorectal cancer cell line CT26 were established and randomly divided into the treatment and control groups.In the treatment group,the animals were injected with CLI-095 （3 mg/kg）, a TLR4 signaling pathway blocker and those in the control group were injected with the equivalent dose of DM-SO.Growth curves of the implanted tumors were measured.Pathological changes of the implanted tumors were observed by HE staining.The apoptosis of the implanted tumors was detected by TUNEL staining.The expres-sion levels of TLR4,cleaved caspase-3 and alternative proteins were determined by Western blot.Results Mean tumor size in the treatment group was （2.39 ±0.32）cm^3 ,significantly larger than （1.77 ±0.25）cm^3 in the control group （t =3.817,P =0.004）.The tumor cells in the treatment group were arranged at a high density and merely partial necrosis was observed,whereas those in the control group were distributed at a low density in disorder and severe necrosis was noted.In the treatment group,the apoptosis index of tumor tissues was （9.86 ±2.80）%,significantly lower compared with （22.57 ±4.93）% in the control group （t =-7.091,P 〈0.001）.The expression of TLR4 protein in tumor tissue did not significantly differ between two groups （P 〉0.05）,whereas the expression of cleaved caspase-3 protein in the treatment group was significant-ly lower than that in the control group.Conclusion Blocking TLR4 signal pathway can inhibit the apoptosis of the tumors of colorectal cancer cell line CT26 impalnted in nude mice and promote the growth of tumors.

关 键 词：结肠癌 TLR4 细胞凋亡 种植瘤 

分 类 号：R735.35[医药卫生—肿瘤]