title: IL-6 mediates the signal pathway of JAK-STAT3-VEGF-C promoting growth, invasion and lymphangiogenesis in gastric cancer.
abstract: Gastric cancer shows the highest invasive and metastasis features, especially lymph metastasis, which is closely associated with poor prognosis of gastric cancer. Although there is evidence that interleukin-6 (IL-6) can promote gastric cancer progression, the underlying specific mechanisms and the mechanisms of gastric cancer lymphangiogenesis are largely unknown. In the present study, we explore whether IL-6 could promote the proliferation and invasion activity of gastric cancer cells, and whether IL-6 mediating VEGF-C production affected the lymphangiogenesis in gastric cancer cells. Our results revealed that IL-6 and its receptors (IL-6 and gp130) are broadly expressed in various gastric cancer cell lines including SGC-7901, MGC, MKN-28 and AGS. Exogenous IL-6 increased the ability of gastric cancer cell proliferation and invasion, which could be weakened by AG490. in addition, exogenous IL-6 promoted the VEGF-C production of gastric cancer cells and the lymphangiogenesis of HDLECs. As we expected, AG490 was able to reduce these effects. Western blot analysis showed that IL-6 increased JKA, STAT3, p-STAT3 and VEGF-C protein levels in the gastric cancer cells. However, the JKA, STAT3, p-STAT3 and VEGF-C protein expression levels were inhibited by AG490. Our data suggested that IL-6 mediates the singnal pathway of JAK-STAT3-VEGF-C promoting the growth, invasion and lymphangiogenesis in gastric cancer. Thus, IL-6 and its related signal pathways may be a promising target for treatment of gastric cancer growth and lymphangiogenesis.
authors.affiliation: Department of Oncology Surgery, Mindong Hospital Affiliated to Fujian Medical University, Fuan, Fujian, P.R. China.
authors.forename: Guibin
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of Gastrointestinal Surgery, First Hospital Affiliated to Fujian Medical University, Fuzhou, Fujian, P.R. China.
authors.forename: Guangwei
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Department of Gastrointestinal Surgery, First Hospital Affiliated to Fujian Medical University, Fuzhou, Fujian, P.R. China.
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Gastrointestinal Surgery, First Hospital Affiliated to Fujian Medical University, Fuzhou, Fujian, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Gastrointestinal Surgery, First Hospital Affiliated to Fujian Medical University, Fuzhou, Fujian, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Hua
authors.affiliation: Department of Gastrointestinal Surgery, First Hospital Affiliated to Fujian Medical University, Fuzhou, Fujian, P.R. China.
authors.forename: Shugang
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Gastrointestinal Surgery, First Hospital Affiliated to Fujian Medical University, Fuzhou, Fujian, P.R. China.
authors.forename: Jinfu
authors.initials: J
authors.lastname: Zhuang
authors.affiliation: Department of Gastrointestinal Surgery, First Hospital Affiliated to Fujian Medical University, Fuzhou, Fujian, P.R. China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Ye
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D050822:Cytokine Receptor gp130 / Q000096:biosynthesis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics*; D053612:Janus Kinases / Q000235:genetics; D042583:Lymphangiogenesis / Q000235:genetics*; D008207:Lymphatic Metastasis; D009361:Neoplasm Invasiveness / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D042582:Vascular Endothelial Growth Factor C; D050822:Cytokine Receptor gp130; D053612:Janus Kinases