The Mechanistic Study Of Gro-α Induced Stromal Fibroblast Senescence In Cervical Tumor Microenvironment

[Background and Purpose] Studies have shown that epithelial cancer can induce senescence of normal stromal fibroblasts and senescent fibroblasts can promote tumor growth. In this study, we detected the expression of GRO-a in stromal fibroblasts of cervical cancer, which may help us to understand the mechanism of cervical cancer, and to provide more adequate theoretical and experimental basis for early clinical diagnosis and treatment of the disease.[Methods] Histological staining of cervical cancer tissue and normal cervical tissue was used to show stromal fibroblasts, epithelial cancer cells, and normal squamous epithelial cells. Identification of stromal cells and examination of HPV infection were also performed. ELISA was used to detect the expression of GRO-a in NFs and CAFs, and also the secretive expression of both IL-6 and VEGF in NFs and CAFs; (3-Galactosidase activity was examined to detect the cellular senescence of NFs and CAFs. The cell growth curve was drawn by cell counting. Western blot was used to detect the expression of VEGF and p16; RT-PCR was used to detect the expression of the GRO-a receptor CXCR2; (3-Galactosidase activity was detected to examine the cell senescence of NFs after treatment with GRO-a, Western blot was used to analyze the probable mechanism and the detailed signal pathway in NFs that were treated with CAF-CM (conditioned medium), CAF-CM+GRO-a Ab, and GRO-a, respectively.[Results] The expression of GRO-a was much more in conditioned medium of CAFs than in that of NFs, and the expression of both IL-6 and VEGF was higher in CAFs than in NFs (P< 0.05). The blue staining of SA-(3-gal and the expression of p16 and VEGF were stronger in CAFs than in NFs. The expression of the GRO-a receptor CXCR2 was higher in CAFs than in NFs. Treatment of NFs with GRO-a induced senescence. Signal pathways involved in the function of GRO-a in tumor microenvironment were found mainly through PI3K/AKT, MAPK, and NF-κB molecules.[Conclusion] Our results provide that GRO-a is rich in cervical tumor microenvironment and GRO-a induces stromal fibroblast senescence, and fibroblast senescence could be induced through PI3K/AKT, MAPK, and NF-κB associated signal pathways which may promote cervical cancer initiation and development.