Previously, we identified differentially expressed proteins, including ADFP, between lung adenocarcinoma (LAC) tissue and paired normal bronchioloalveolar epithelium. In this study, we investigated the role of ADFP in LAC. ADFP levels in the serum of patients with lung cancer and benign diseases were measured by enzyme‐linked immunosorbent assays (ELISA). shRNA was used to knock‐down or overexpress ADFP in A549 and NCI‐H1299 cells. The biological function of ADFP and its underlying mechanisms was evaluated in vivo and in vitro. ADFP was highly expressed in the serum of lung cancer patients, especially those with LAC. ADFP promoted cell proliferation and up‐regulated the p‐Akt/Akt ratio in A549 and NCI‐H1299 cells in vitro. Furthermore, in nude mice, ADFP promoted tumour formation with high levels of p‐Akt/Akt, Ki67 and proliferating cell nuclear antigen (PCNA). Similar to the effect of ADFP knock‐down, MK‐2206 (a phosphorylation inhibitor of Akt) reduced A549 and NCI‐H1299 cell proliferation. In ADFP‐overexpressing A549 and NCI‐H1299 cells, proliferation was suppressed by MK‐2206 and returned to the control level. ADFP did not regulate invasion, migration or adhesion in LAC cells. Together, these results suggest that ADFP promotes LAC cell proliferation in vitro and in vivo by increasing Akt phosphorylation level.

中文翻译：

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ADFP通过Akt磷酸化促进肺腺癌细胞增殖

以前，我们在肺腺癌 (LAC) 组织和配对的正常细支气管肺泡上皮之间鉴定了差异表达的蛋白质，包括 ADFP。在这项研究中，我们调查了 ADFP 在 LAC 中的作用。通过酶联免疫吸附试验（ELISA）测量肺癌和良性疾病患者血清中的 ADFP 水平。shRNA 用于在 A549 和 NCI-H1299 细胞中敲低或过表达 ADFP。ADFP 的生物学功能及其潜在机制在体内和体外进行了评估。ADFP在肺癌患者尤其是LAC患者的血清中高表达。ADFP 在体外促进 A549 和 NCI-H1299 细胞中的细胞增殖并上调 p-Akt/Akt 比率。此外，在裸鼠中，ADFP 促进了具有高水平 p-Akt/Akt 的肿瘤形成，Ki67 和增殖细胞核抗原 (PCNA)。与 ADFP 敲低的效果相似，MK-2206（Akt 的磷酸化抑制剂）降低了 A549 和 NCI-H1299 细胞的增殖。在过表达 ADFP 的 A549 和 NCI-H1299 细胞中，MK-2206 抑制增殖并恢复到对照水平。ADFP 不调节 LAC 细胞的侵袭、迁移或粘附。总之，这些结果表明 ADFP 通过增加 Akt 磷酸化水平在体外和体内促进 LAC 细胞增殖。