Introduction: Trefoil Factor (TFF) is a member of a protein family comprised of three isoforms, of which TFF-1 exhibits antithetical functions; promotion or suppression of cell proliferation, survival and invasion, depending on the cancer type. However, the pathobiological function of TFF-1 in lung carcinoma has been still unclear.
Methods: We examined the expression and secretion of TFF-1 using cultured human lung carcinoma cells by immunoblotting, immunofluorescence, enzyme-linked immunosorbent assay and quantitative real-time PCR analyses. The effects of TFF-1 on various phenotypes were analyzed in two cell lines, including those transfected with cDNA encoding TFF-1. Cell proliferation and death were examined by hemocytometer cell counting and by colorimetric viability/cytotoxicity assay. Cell cycle profile, migration and invasion were also examined by flow cytometry, wound healing assay and Matrigel Transwell assay, respectively. The effect of TFF-1 overexpression was confirmed by additional transfection of TFF-1-specific siRNA.
Results: Endogenous TFF-1 protein expression and secretion into the media were observed exclusively in adenocarcinoma-derived cell lines. Forced overexpression of TFF-1 drove cell cycle transition, while the proliferation decreased by 19% to 25% due to increased cell death. This cell death was predominantly caused by apoptosis, as assessed by the activation of caspase 3/7. Cell migration was also suppressed by 71% to 82% in TFF-1-transfected cells. The suppressive effect of TFF-1 on proliferation and migration was restored by transfection of TFF-1 siRNA. Moreover, invasion was also suppressed to 77% to 83% in TFF-1-transfected cells.
Conclusion: These findings reveal that TFF-1 functions as a suppressor of cancer proliferation by induction of apoptosis, cell migration and invasion and thus may provide a synergistic target for potential treatment strategies for human lung carcinoma.

Keywords: TFF-1, lung carcinoma cells, growth inhibition, apoptosis, migration, invasion


中文翻译：

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TFF-1 抑制与肺癌进展相关的多种表型的功能

简介：三叶因子 (TFF) 是由三种同工型组成的蛋白质家族的成员，其中 TFF-1 具有相反的功能；根据癌症类型，促进或抑制细胞增殖、存活和侵袭。然而，TFF-1在肺癌中的病理生物学功能仍不清楚。
方法：我们使用培养的人肺癌细胞通过免疫印迹、免疫荧光、酶联免疫吸附测定和定量实时 PCR 分析检查了 TFF-1 的表达和分泌。在两个细胞系中分析了 TFF-1 对各种表型的影响，包括用编码 TFF-1 的 cDNA 转染的细胞系。通过血细胞计数器细胞计数和比色活力/细胞毒性测定检查细胞增殖和死亡。还分别通过流式细胞术、伤口愈合测定和 Matrigel Transwell 测定检查细胞周期谱、迁移和侵袭。TFF-1 过表达的影响通过额外转染 TFF-1 特异性 siRNA 得到证实。
结果：仅在腺癌细胞系中观察到内源性 TFF-1 蛋白表达和分泌到培养基中。TFF-1 的强制过表达驱动细胞周期转变，而由于细胞死亡增加，增殖减少了 19% 至 25%。如通过 caspase 3/7 的激活所评估的，这种细胞死亡主要由细胞凋亡引起。在 TFF-1 转染的细胞中，细胞迁移也被抑制了 71% 到 82%。通过转染 TFF-1 siRNA，TFF-1 对增殖和迁移的抑制作用得以恢复。此外，在 TFF-1 转染的细胞中，侵袭也被抑制到 77% 到 83%。
结论：这些发现表明，TFF-1 通过诱导细胞凋亡、细胞迁移和侵袭而起到抑制癌症增殖的作用，因此可能为人类肺癌的潜在治疗策略提供协同靶点。

关键词： TFF-1，肺癌细胞，生长抑制，凋亡，迁移，侵袭