Department of Endoscopy Center, The First Affiliated Hospital of Xiamen University, Xiamen, China.
Department of Gastrointestinal Surgery, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, China.
J Cell Physiol. 2019 Apr;234(4):3613-3620. doi: 10.1002/jcp.27083. Epub 2018 Nov 22.
Leukemia inhibitory factor (LIF), a member of the interleukin-6 cytokine family, plays a complex role in cancer. LIF inhibits the proliferation and survival of several myeloid leukemia cells but promotes tumor progression and metastasis in many solid tumors. However, the relationship between LIF and gastric cancer has not been well understood. LIF was downregulated in gastric cancer as detected by western blot analysis and immunohistochemistry (IHC). Notably, LIF was downregulated in approximately 70% (56/80) of primary gastric cancers, in which it was significantly associated with advanced clinical stage, lymph node metastasis, and poor overall survival (median 5-year survival = 26 vs. 43 months for patients with high LIF expression and low LIF expression gastric cancer, respectively). To study the potential function of LIF in the downregulation of gastric cancer, we monitored the behavior using proliferation, cell cycle, and flow cytometry analysis. Overexpression of LIF inhibited the gastric cancer cell cycle in the G1 phase. In our experiment, overexpression of LIF by lentivirus upregulated P21 and downregulated cyclin D1. Recombinant human LIF also downregulated P21 and cyclin D1 at various times. A further in vivo tumor formation study in nude mice indicated that overexpression of LIF in gastric cancer significantly delayed the progress of tumor formation. These findings indicate that LIF may serve as a negative regulator of gastric cancer.
白血病抑制因子（LIF）是白细胞介素-6 细胞因子家族的一员，在癌症中发挥着复杂的作用。LIF 抑制几种髓样白血病细胞的增殖和存活，但促进许多实体瘤的肿瘤进展和转移。然而，LIF 与胃癌之间的关系尚未得到很好的理解。通过 Western blot 分析和免疫组织化学（IHC）检测到胃癌中 LIF 下调。值得注意的是，在大约 70%（56/80）的原发性胃癌中 LIF 下调，其与晚期临床分期、淋巴结转移和总体生存率差显著相关（中位 5 年生存率分别为高 LIF 表达和低 LIF 表达胃癌患者的 26 个月和 43 个月）。为了研究 LIF 在胃癌下调中的潜在功能，我们通过增殖、细胞周期和流式细胞术分析监测其行为。LIF 的过表达抑制了胃癌细胞周期的 G1 期。在我们的实验中，慢病毒过表达 LIF 上调了 P21 并下调了 cyclin D1。重组人 LIF 也在不同时间下调了 P21 和 cyclin D1。在裸鼠体内进一步的肿瘤形成研究表明，胃癌中 LIF 的过表达显著延缓了肿瘤形成的进展。这些发现表明 LIF 可能作为胃癌的负调节剂。
