Gynecology Department, Changning Maternity and Infant Health Hospital, 773#, Wuyi Rd., Shanghai, 200051, China.
Mol Cell Biochem. 2018 Nov;448(1-2):311-320. doi: 10.1007/s11010-018-3335-7. Epub 2018 Mar 8.
Upregulation of A-kinase-interacting protein 1 (AKIP1) has been observed in breast and esophageal cancers, indicating that AKIP1 may be a potent oncogenic protein. However, the role of AKIP1 in cervical cancer still remains unknown. This study aimed to explore the role of AKIP1 in cervical cancer and to investigate the underlying mechanism of AKIP1 in tumor growth. Expression of AKIP1 in cervical cancer cells was determined by qRT-PCR and western blotting. Cell-Light EdU and colony formation assays were used to determine cell proliferation. CXCL1 and CXCL8 proteins were quantified by ELISA kits. Western blotting and qRT-PCR were used to examine the alterations in signaling-related proteins and mRNA, respectively. Endothelial cell tube formation assay was performed to evaluate the effect of AKIP1 on angiogenesis. A BALB/c nude mouse xenograft model was used to evaluate the role of AKIP1 in vivo. Cancer cell proliferation was inhibited and tumor growth and angiogenesis restrained in BALB/c nude mice by suppressing AKIP1 expression in cervical cancer cell lines. In addition, overexpression of AKIP1 in cervical cancer cells elevated the levels of CXCL1, CXCL2, and CXCL8. These three chemokines were not only involved in endothelial tube formation by binding to the endothelial receptor CXCR2, but also in cervical cancer cell proliferation and clone formation, which were induced by overexpression of AKIP1. Furthermore, we found that AKIP1-induced chemokine expression was decreased by an inhibitor of nuclear factor kappa-B kinase subunit β. These results show that AKIP1 is crucial in cervical cancer angiogenesis and growth by elevating the levels of the NF-κB-dependent chemokines CXCL1, CXCL2, and CXCL8.
AKIP1（A-kinase-interacting protein 1）的上调已在乳腺癌和食管癌中观察到，表明 AKIP1 可能是一种有效的致癌蛋白。然而，AKIP1 在宫颈癌中的作用仍不清楚。本研究旨在探讨 AKIP1 在宫颈癌中的作用，并研究 AKIP1 在肿瘤生长中的潜在机制。通过 qRT-PCR 和 Western blot 测定 AKIP1 在宫颈癌细胞中的表达。使用 Cell-Light EdU 和集落形成测定法测定细胞增殖。通过 ELISA 试剂盒定量测定 CXCL1 和 CXCL8 蛋白。使用 Western blot 和 qRT-PCR 分别检测信号相关蛋白和 mRNA 的变化。进行内皮细胞管形成测定以评估 AKIP1 对血管生成的影响。使用 BALB/c 裸鼠异种移植模型评估 AKIP1 在体内的作用。通过抑制宫颈癌细胞系中 AKIP1 的表达，抑制了癌细胞的增殖，抑制了 BALB/c 裸鼠的肿瘤生长和血管生成。此外，过表达 AKIP1 可提高宫颈癌细胞中 CXCL1、CXCL2 和 CXCL8 的水平。这三种趋化因子不仅通过与内皮细胞受体 CXCR2 结合参与内皮细胞管形成，而且还参与了 AKIP1 过表达诱导的宫颈癌细胞增殖和克隆形成。此外，我们发现核因子 kappa-B 激酶亚单位β抑制剂可降低 AKIP1 诱导的趋化因子表达。这些结果表明，AKIP1 通过上调 NF-κB 依赖性趋化因子 CXCL1、CXCL2 和 CXCL8，在宫颈癌的血管生成和生长中起着关键作用。
