Interleukin-8 promotes integrin β3 upregulation and cell invasion through PI3K/Akt pathway in hepatocellular carcinoma
Interleukin-8 promotes integrin β3 upregulation and cell invasion through PI3K/Akt pathway in hepatocellular carcinoma
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Interleukin-8通过PI3K/Akt通路促进肝细胞癌整合素β3上调和细胞侵袭
DOI：
10.1186/s13046-019-1455-x
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发表时间：
2019-11-04
影响因子：
11.3
通讯作者：
Liu, Jun
中科院分区：
文献类型：
--
作者：
Sun, Fengkai;Wang, Jianping;Liu, Jun
研究背景白介素8（IL-8）在肝细胞癌（HCC）的侵袭和转移中发挥着重要作用，与HCC患者的不良预后密切相关。整合素αvβ3是整合素家族的成员，据报道在癌组织中过度表达并介导肝癌细胞的侵袭和转移。然而，IL-8和整合素αvβ3在HCC中的关系以及IL-8和整合素αvβ3在HCC侵袭中的潜在机制仍不清楚。方法采用实时荧光定量PCR、Western blot、免疫组化等方法检测HCC细胞和组织中IL-8、整合素αv和整合素β3的表达。采用Transwell实验和Western blot检测IL-8敲低或外源IL-8预处理的HCC细胞的侵袭能力、整合素β3的表达以及PI3K/Akt通路的激活。结果 与低转移细胞系相比，高转移 HCC 细胞系中 IL-8、整合素 α v 和整合素 β 3 过表达。 HCC组织中整合素β3与IL-8的表达呈正相关。 IL-8 siRNA 转染降低了 HCC 细胞侵袭以及整合素 β 3、p-PI3K 和 p-Akt 的水平。 CXCR1 siRNA 或 CXCR2 siRNA 转染可显着抑制 IL-8 诱导的 HCC 细胞侵袭和整合素 β 3 表达。当我们用外源性IL-8刺激HCC细胞时，细胞侵袭以及整合素β3、p-PI3K和p-Akt水平增加，通过添加PI3K抑制剂LY294002可以有效逆转这种情况。结论 我们的结果表明，IL-8 通过激活 PI3K/Akt 通路促进整合素 β 3 上调和 HCC 细胞的侵袭。 IL-8/CXCR1/CXCR2/PI3K/Akt/整合素β3轴可能作为HCC患者的潜在治疗靶点。
Background Interleukin-8 (IL-8) plays a vital role in the invasion and metastasis of hepatocellular carcinoma (HCC), and is closely associated with poor prognosis of HCC patients. Integrin alpha v beta 3, a member of the integrin family, has been reported to be overexpressed in cancer tissues and mediate the invasion and metastasis of HCC cells. However, the relationship between IL-8 and integrin alpha v beta 3 in HCC and the underlying mechanism of IL-8 and integrin alpha v beta 3 in the invasion of HCC remains unclear. Methods The expression of IL-8, integrin alpha v and integrin beta 3 in HCC cells and tissues was detected by quantitative real-time PCR, Western blot and immunohistochemistry. Transwell assay and Western blot was used to detect the invasiveness, the expression of integrin beta 3 and the activation of PI3K/Akt pathway of HCC cells pretreated with IL-8 knockdown or exogenous IL-8. Results IL-8, integrin alpha v and integrin beta 3 were overexpressed in highly metastatic HCC cell lines compared with low metastatic cell lines. There was a positive correlation between integrin beta 3 and IL-8 expression in HCC tissues. IL-8 siRNA transfection reduced HCC cell invasion and the levels of integrin beta 3, p-PI3K and p-Akt. IL-8 induced HCC cell invasion and integrin beta 3 expression was significantly inhibited by transfection with CXCR1 siRNA or CXCR2 siRNA. When we stimulated HCC cells with exogenous IL-8, cell invasion and the levels of integrin beta 3, p-PI3K, and p-Akt increased, which could be effectively reversed by adding PI3K inhibitor LY294002. Conclusions Our results suggest that IL-8 promotes integrin beta 3 upregulation and the invasion of HCC cells through activation of the PI3K/Akt pathway. The IL-8/CXCR1/CXCR2/PI3K/Akt/integrin beta 3 axis may serve as a potential treatment target for patients with HCC.