The Effects And Mechanism Of PDGF-BB Expression In Esophageal Cancer Treated With Radiotherapy

Background: Esophageal cancer(EC)is a highly common and aggressive tumor which is a leading cause of cancer-related deaths worldwide.And China has the highest incidence and mortality rate of EC in the world,which accounts for more than half of the global total.Radiotherapy is the major approach and is well tolerated in locally advanced esophageal squamous cell carcinoma(ESCC).And nowadays,no effective biological markers have been identified for predicting the prognosis of patients with ESCC.Platelet-derived growth factor(PDGF)is associated with a poor prognosis of various malignancies.The present study aimed to assess the effect of PDGF-BB on radiotherapeutic responses of ESCC and the underlying mechanisms of its roles in ESCC.Patients and methods: Serum from 68 cases that received neoadjuvant or radical radiotherapy were obtained before and during radiotherapy.Gene expression analyses were validated by enzyme linked immunosorbant assay(ELISA).In addition,immunohistochemistry(IHC)was applied to detect the expression of PDGF-BB in ESCC tissue specimens from patients and normal adjacent operative tissue specimens of the remaining four patients.We also assessed the inhibitory effect and radio-sensitivity of PDGFB on KYSE30 and KYSE150 cell-lines by flow cytometric analysis,the Cell Counting Kit-8(CCK-8),colony formation and transwell assays in cellular experiments.In addition,Western immunoblotting analysis was used to detect the effects of radiotherapy on the Phosphatidylinositol 3-kinase / Protein Kinase B(PI3K / AKT)pathway.Results: The prognosis of patients with significantly reduced PDGF-BB was probably better than that of the others found in the progression-free survival(PFS)and overall survival(OS)groups.Tumor location and concurrent chemotherapy may also represent significant prognostic factors.The change rate of PDGF-BB was probably associated with response to radiotherapy.For tissue samples analyzed by IHC,we found that PDGF-BB was over-expressed in 41 of 66 ESCC cases without chemoradiotherapy(62.1%)while it was over-expressed in only 17 of 41 ESCC cases after neoadjuvant chemoradiotherapy(41.5%).And the expression was negative in four normal adjacent operative tissues.Depletion of PDGFB significantly suppressed the proliferation,invasion and migration of cancer cells.Inhibiting PDGFB induced cellular apoptosis and promoted the sensitivity to ionizing radiation(IR).Furthermore,IR inhibited PDGF-BB-induced migration by blocking the PI3 K / AKT pathway in ESCC cells.Conclusions: We found that the expression of PDGF-BB provided a possible model for predicting ESCC radiotherapy.It can also be used as a prognostic indicator for locally advanced ESCC that was treated by radiotherapy.Clinical Trail: A Phase II Trail to Compare Efficacy and Safety of CRT VS Neo-CRT in Patients Who Achieved CCR for Esophageal Cancer ID: NCT02959385 Protocol ID: CIH-PQS-2016090001...