Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Department of Pathology, The Second Affiliated Hospital, Xi'an JiaoTong University, Xi'an, Shaanxi, China.
J Cell Mol Med. 2021 Jan;25(2):827-839. doi: 10.1111/jcmm.16136. Epub 2020 Nov 29.
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.
先前，我们鉴定出肺腺癌（LAC）组织与配对正常细支气管肺泡上皮之间差异表达的蛋白质，包括 ADFP。在这项研究中，我们研究了 ADFP 在 LAC 中的作用。通过酶联免疫吸附测定（ELISA）测量肺癌和良性疾病患者血清中的 ADFP 水平。使用 shRNA 在 A549 和 NCI-H1299 细胞中敲低或过表达 ADFP。在体内和体外评估 ADFP 的生物学功能及其潜在机制。ADFP 在肺癌患者的血清中高表达，尤其是在 LAC 患者中。ADFP 在体外促进 A549 和 NCI-H1299 细胞的增殖，并上调 p-Akt/Akt 比值。此外，在裸鼠中，ADFP 促进肿瘤形成，p-Akt/Akt、Ki67 和增殖细胞核抗原（PCNA）水平较高。与 ADFP 敲低的作用相似，MK-2206（Akt 的磷酸化抑制剂）降低了 A549 和 NCI-H1299 细胞的增殖。在 ADFP 过表达的 A549 和 NCI-H1299 细胞中，MK-2206 抑制增殖并恢复至对照水平。ADFP 不调节 LAC 细胞的侵袭、迁移或黏附。综上所述，这些结果表明 ADFP 通过增加 Akt 磷酸化水平促进体外和体内 LAC 细胞的增殖。
