Heregulin通过Her2激活SKBR3细胞内IKK/NF-κB信号通路  

Heregulin activates IKK/NF-κB signal pathway via Her2 in SKBR3 cell lines

作　　者：金波[1] 邱慧玲[1] 李玉萍[1] 

机构地区：[1]中国人民解放军第一七四医院,厦门大学附属成功医院妇科,福建厦门361001

出　　处：《现代肿瘤医学》2017年第4期535-539,共5页Journal of Modern Oncology

摘　　要：目的:初探Her2激动剂Heregulin(HRG)对人乳腺癌SKBR3细胞内IKK/NF-κB信号通路的激活机制。方法:Western blotting法检测HRG对SKBR3细胞中PI3K/Akt/IKK信号通路的影响。以TNF-α/RIP1/IKK这条经典信号通路为对照,引入各通路中关键蛋白(PI3 K、RIP1及IKK)的抑制剂,对比各抑制剂对两条通路的影响。实时无标记细胞分析技术监测HRG对SKBR3细胞增殖的促进作用及IKK抑制剂TPCA1对HRG的拮抗作用。结果:HRG与TNF-α均能激活IKK引起NF-κB入核,RIP1的抑制剂Necrostatin-1能阻断由TNF-α引起的IKK活化,但不能阻断由HRG引起的IKK活化,表明HRG并非通过传统的途径激活IKK。PI3K抑制剂LY294002能阻断由HRG引起的IKK激活,PI3K是Her2信号通路的关键蛋白之一,因此推测HRG是经由PI3K/Akt信号通路,完成对IKK/NF-κB通路的激活。细胞生长曲线反映,HRG能促进SKBR3细胞的增殖,TPCA1对HRG具有拮抗作用,对数期细胞经100 nmol/L的TPCA1处理后,细胞增殖受到抑制,数量迅速下降。结论:HRG可以通过Her2/PI3K/Akt途径激活SKBR3细胞内IKK/NF-κB信号通路。Objective： To study the activation mechanism of IKK /NF- κB signaling pathway which induced by Her2 agonist Heregulin（ HRG） in human breast cancer SKBR3 cells. Methods： Western blotting method was used to detect the effect of HRG on PI3 K / Akt / IKK signaling pathway in SKBR3 cells. Taken the classic signal pathway TNF- α / RIP1 / IKK as a control,the inhibitors of key protein（ PI3 K,RIP1 and IKK） in various pathways were introduced to study the relationship between IKK / NF- κB and HRG. The effect of HRG on the proliferation of SKBR3 cells and the antagonistic effect of IKK inhibitor TPCA1 on HRG were monitored by real time non labeled cell analysis technique. Results： Both HRG and TNF- α could promote NF- κB into the nucleus by activating IKK. RIP1 inhibitor Necrostatin- 1 could block the activation of IKK which induced by TNF- α,but was invalid for HRG,which indicated that HRG was able to activate IKK via non- traditional pathways. The activation of IKK which activated by HRG could be blocked by PI3 K inhibitor LY294002,in addition,PI3 K was one of primary proteins in Her2 pathway,so,we speculated that HRG could activate IKK / NF- κB pathway via the PI3 K / Akt signaling pathway. The cell growth curve showed that HRG could promote the proliferation of SKBR3 cells and TPCA1 was able to reserve its effect,when treated with 100 nmol / L TPCA1 in logarithmic phase,and the proliferation rate of SKBR3 cells decreased rapidly. Conclusion： HRG can promote the activation of NF- κB signaling pathway in SKBR3 cells through the Her2 / PI3 K / Akt pathway.

关 键 词：SKBR3细胞 HRG PI3K IKK NF-ΚB 

分 类 号：R737.9[医药卫生—肿瘤]