关键词: 白细胞介素-6, 信号转导和转录激活因子3, 大细胞肺癌, 机制

Abstract: Background and purpose: Interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3) pathway is overactivated and overexpressed in many malignant tumors, including leukemia, head and neck squamous cell carcinoma, multiple melanoma, breast cancer, and prostate cancer. However, it is rare in the study of large cell lung cancer. The aim of this study was to investigate the effects and mechanisms of IL-6/STAT3 signaling pathway related genes and the downstream genes in large cell lung cancer NL9980 cell lines. Methods: Various concentrations of IL-6 were administered to 5 groups of NL9980 cell lines respectively (0, 1.0, 5.0, 10.0 and 20.0 ng/mL). The changes of proliferation of the NL9980 cell lines were detected by methylthiazol tetrazolium (MTT) assay. Real-time PCR was used to detect mRNA expression changes of the IL-6/STAT3 pathway related genes (including IL-6 and STAT3 genes) and the downstream genes Bcl-2, VEGF, CYCD1. Correlation test with IL-6/STAT3 was done. Results: IL-6 could promote the proliferation of NL9980 cells lines, and the optimal concentration was 5 ng/mL (F=8.11, P<0.05). Various concentrations of IL-6 were administered to NL9980 cell lines. Expressions of IL-6 and STAT3 genes showed obvious increases (4.78±0.09, 5.17±0.05, P<0.05), and the peak level was found in the 5 ng/mL group. The downstream genes Bcl-2, VEGF, CYCD1 also showed obvious increases (4.52±0.14, 4.12±0.12, 3.98±0.17), the peak level was found in the 5 ng/mL group, and other groups did not change significantly (P>0.05). Correlation test showed Bcl-2, VEGF, CYCD1 genes were correlated with IL-6 (r=0.952, r=0.836, r=0.880) and STAT3 (r=0.995, r=0.746, r=0.800) positively. Conclusion: IL-6 could promote the apoptosis of NL9980 cells via activating IL-6/STAT3 signaling pathway and upregulating the downstream genes Bcl-2, VEGF, CYCD1.

Key words: Interleukin-6, STAT3, Large cell lung cancer, Mechanism