Abstract

C-X-C motif chemokine ligand 14 (CXCL14) has antitumor effect. Kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway is activated in various tumors. The relationship between CXCL14 and Akt/mTOR pathway in hepatocellular carcinoma (HCC) remained elusive. Therefore, this paper aimed to examine their interaction in HCC. First, CXCL14 expression was determined to be low-expressed in HCC tissues and cells (SNU-423, SNU-182, SNU-387, PLC/PRF/5, HuH7, and HCCLM3). Then, CXCL14 was overexpressed in HuH7 cells and inhibited in HCCLM3 cells to help investigate the function of CXCL14 on cell viability, growth and apoptosis. Akt activator (SC79) and inhibitor (AZD5363) were used to examine the involvement of Akt pathway in hepatocellular carcinoma. Overexpressed CXCL14 suppressed cell viability and growth, but promoted the apoptosis by upregulated Bax and cleaved(C) caspase-3, donwregulated Bcl-2 and the inhibition of Akt and mTOR phosphorylation. Meanwhile, knockdown of CXCL14 imposed an opposite effect to overexpressed CXCL14. SC79 partially mitigated the functions of overexpressed CXCL14, while AZD5363 mitigated the functions of CXCL14 knockdown. To conclude, CXCL14 inhibited growth but promoted apoptosis of HCC cells via suppressing Akt/mTOR pathway, thus, CXCL14 might be a potential target for HCC treatment in clinical practice.

摘要

CXC 基序趋化因子配体 14 (CXCL14) 具有抗肿瘤作用。激酶 B (Akt)/哺乳动物雷帕霉素靶标 (mTOR) 途径在各种肿瘤中被激活。CXCL14 和 Akt/mTOR 通路在肝细胞癌 (HCC) 中的关系仍然难以捉摸。因此，本文旨在研究它们在 HCC 中的相互作用。首先，CXCL14 表达被确定为在 HCC 组织和细胞（SNU-423、SNU-182、SNU-387、PLC/PRF/5、HuH7 和 HCCLM3）中低表达。然后，CXCL14 在 HuH7 细胞中过表达并在 HCCLM3 细胞中被抑制，以帮助研究 CXCL14 对细胞活力、生长和凋亡的功能。Akt 激活剂 (SC79) 和抑制剂 (AZD5363) 用于检查 Akt 通路在肝细胞癌中的参与。过表达的 CXCL14 抑制细胞活力和生长，但通过上调 Bax 和 cleaved(C) caspase-3、下调 Bcl-2 以及抑制 Akt 和 mTOR 磷酸化来促进细胞凋亡。同时，CXCL14 的敲低对过表达的 CXCL14 产生了相反的影响。SC79 部分减轻了过表达 CXCL14 的功能，而 AZD5363 减轻了 CXCL14 敲低的功能。总之，CXCL14通过抑制Akt/mTOR通路抑制HCC细胞的生长但促进细胞凋亡，因此CXCL14可能是临床实践中HCC治疗的潜在靶点。