JNK信号通路在大肠癌侵袭和转移中的作用及机制  

Mechanisms underlying the role of JNK signaling pathway in the invasion and metastasis of colon cancer cells

作　　者：周燕红[1] 何小飞[1] 高卉[1] 王瑶芬[1] 

机构地区：[1]咸宁学院医学院消化内科,湖北省咸宁市437100

出　　处：《世界华人消化杂志》2009年第21期2142-2146,共5页World Chinese Journal of Digestology

基　　金：湖北省卫生厅基金资助项目;No.JX3C11~~

摘　　要：目的:观察c-Jun氨基末端激酶(c-jun-N-terminal kinase,JNK)信号通路的活化对大肠癌细胞运动、侵袭的影响,并探讨大肠癌转移可能的分子机制.方法:LoVo细胞无血清饥饿24h同步化后,对照组无纤维粘连蛋白(fibronectin,FN)干预,FN组给予FN10,20,40mg/L,24h干预.JNK抑制剂组给予FN40mg/L+SP600125(20,40μmol/L)干预24h.用Boyden小室法检测其体外运动和侵袭能力.Westernblot法检测JNK磷酸化和MMP-9蛋白质表达.结果:FN可剂量性增加LoVo细胞运动和侵袭细胞数,SP600125能明显减少FN诱导的细胞运动和侵袭力.与对照组相比,FN40mg/L干预时p-JNK和MMP-9明显增高(38.39%±5.97%vs28.61%±4.19%;58.25%±6.53%vs33.43%±2.05%,均P<0.01).与FN40mg/L组相比,SP60012540μmol/L能明显抑制p-JNK和MMP-9蛋白的表达(29.59%±2.17%vs38.39%±5.97%,36.69%±4.20%vs58.25%±6.53%,均P<0.01).结论:大肠癌细胞JNK磷酸化可激活其下游成员使大肠癌基质金属蛋白酶的分泌增加,导致大肠癌细胞的运动和侵袭力增加,最终促进癌细胞的转移.AIM：To investigate the effects of c-Jun-N-terminal kinase（JNK）signaling pathway on the migration and invasion of human colon cancer cells（LoVo）stimulated with fibronectin and explore possible mechanisms underlying such effects.METHODS：LoVo cells were cultured in serumfree medium for 24 hours and then divided into normal control group（no fibronectin treatment）,fibronectin treatment group（a 24-hour treatment with fibronectin at concentrations of 10,20 and 40 mg/L,respectively）,and SP600125 treatment group（a 24-hour treatment with 40 mg/L of fi-bronectin and SP600125 at concentrations of 20 and 40 μmol/L, respectively）. The in vitro migration and invasion of LoVo cells were measured by Boyden chamber assay. The phosphorylation levels of JNK and matrix metalloproteinase-9 （MMP-9） were detected by Western blot.RESULTS： Fibronectin significantly increased the migration and invasion of LoVo cells, while SP600125 showed an obvious inhibitory effect on migration and invasion. The expression of p-JNK and MMP-9 in the fibronecfin （40 mg/L） treatment group was more significantly upregulated than that in normal control group （38.39% ± 5.97% vs 28.61% ± 4.19% and 58.25% ± 6.53% vs 33.43% ±2.05%, respectively; both P 〈 0.01）. The upregulation of p-JNK and MMP-9 expression in the SP600125 （40 μmol/L） treatment group was significantly lower than that in the fibronectin （40 mg/L） treatment group （29.59% ± 2.17% vs 38.39% ± 5.97% and 36.69% ± 4.20% vs 58.25% ± 6.53%, both P 〈 0.01）. CONCLUSION： Fibronectin can enhance the migration and invasion of human colon cancer cells perhaps through upregulation of p-JNK and MMP-9 expression.

关 键 词：大肠癌 侵袭 转移 C-JUN氨基末端激酶 纤维粘连蛋白 

分 类 号：R735.34[医药卫生—肿瘤]