Nair S, Mayotte J, Lokshin A, Levitt M
Division of Medical Oncology, University of Pittsburgh School of Medicine, PA 15213-2592.
J Natl Cancer Inst. 1994 Mar 2;86(5):378-83. doi: 10.1093/jnci/86.5.378.
More than 95% of lung cancers occur in the bronchi, appearing as adenocarcinoma, squamous carcinoma, large-cell and small-cell carcinoma, or mixed types. Generally, the least aggressive form is squamous cell lung cancer, suggesting the possibility that promotion of squamous cell differentiation may have therapeutic potential for non-small-cell lung cancer, a disease having no effective systemic therapy. Interferons are a group of glycoproteins with known antiproliferative effects, including the ability to induce differentiation in certain cases.
These studies were conducted to determine whether interferon beta induces squamous cell differentiation in non-small-cell lung cancer in vitro.
NCI-H596 adenosquamous cells were grown to confluence to maximize their differentiation potential. Growth and parameters for squamous differentiation (cross-linked envelope competence, transglutaminase activity, and relative involucrin expression) were then measured when the cells were exposed to various concentrations of interferon beta.
Interferon beta inhibited growth of the NCI-H596 cell line and stimulated envelope competence, involucrin expression, and type 2 transglutaminase activity. Alterations in transglutaminase activity and involucrin expression preceded induction of envelope competence and growth suppression.
Interferon beta suppresses the growth and stimulates markers of squamous differentiation in NCI-H596. While the mechanism(s) for such effects are unknown, the sequence of effects suggests a causal relationship between differentiation induction and subsequent growth suppression.
Interferon beta may have clinical usefulness in squamous differentiation strategies for the treatment of non-small-cell lung cancer. More must be learned about the mechanisms whereby interferons and other biologic agents induce differentiation, and clinical trials will be needed to determine whether in vitro results are pertinent in vivo.
超过95%的肺癌发生于支气管，表现为腺癌、鳞癌、大细胞癌、小细胞癌或混合型。一般来说，侵袭性最小的肺癌类型是鳞状细胞肺癌，这提示促进鳞状细胞分化可能对非小细胞肺癌具有治疗潜力，因为非小细胞肺癌尚无有效的全身治疗方法。干扰素是一组已知具有抗增殖作用的糖蛋白，在某些情况下还具有诱导分化的能力。
进行这些研究以确定β干扰素是否能在体外诱导非小细胞肺癌的鳞状细胞分化。
将NCI-H596腺鳞癌细胞培养至汇合状态以最大化其分化潜能。然后在细胞暴露于不同浓度的β干扰素时，测量其生长情况以及鳞状分化的参数（交联包膜能力、转谷氨酰胺酶活性和相对内披蛋白表达）。
β干扰素抑制NCI-H596细胞系的生长，并刺激包膜能力、内披蛋白表达和2型转谷氨酰胺酶活性。转谷氨酰胺酶活性和内披蛋白表达的改变先于包膜能力的诱导和生长抑制。
β干扰素抑制NCI-H596细胞的生长并刺激其鳞状分化标志物。虽然这种作用的机制尚不清楚，但作用顺序表明分化诱导与随后的生长抑制之间存在因果关系。
β干扰素在非小细胞肺癌的鳞状分化治疗策略中可能具有临床应用价值。关于干扰素和其他生物制剂诱导分化的机制还需要更多了解，并且需要进行临床试验以确定体外结果在体内是否相关。
