Abstract: Objective To investigate the influence of PARG silencing on the tumor lymphangiogenesis. Methods Lentiviral-PARG-shRNA was transfected into mouse colon carcinoma CT26 cell line. The CT26 cells stably expressing PARG gene were established by puromycin selection. The expressions of PARG, PARP-1, NF-κB and VEGF-C protein were detected by Western blot analysis. BALB/c mice benign lymphangiomas in abdominal cavity were induced by injection of 0.2ml incomplete Freund’s adjuvant (IFA, 1:1 with PBS) and mechanically disrupted to obtain LECs. Expressions of VEGFR-3 and Podoplanin were analyzed by immunofluorescence cytochemistry. The capability of LECs to form lymphatic vessel-like structures was detected by a LEC-CT26 cells co-culture method. Results The expression levels of PARP-1, NF-κB, and VEGF-C were reduced in PARG-silencing CT26 cells (P<0.05). Benign lyphangiomas were successfully induced by emulsified IFA. The expressions of VEGFR-3 and Podoplanin were positive in isolated LECs. The lymphatic vessel-like structures in PARG-silencing CT26 cells were significantly less than that in the control group (P < 0.05).Conclusion These studies demonstrate that PARG silencing significantly reduces VEGF-C expression and suppresses the formation of lymphatic vessel-like structures. We therefore propose that PARG silencing has an antilymphangiogentic effect and probably prevent the metastatic dissemination by lymph system.

Key words: PARG, PARP-1, NF-κB, VEGF-C, tumor lymphangiogenesis