The Effect Of PARP Inhibition On The Liver Metastasis Of Mouse Colon Adenocarcinoma CT26 Cell Line In Vivo And Its Mechanism

Objective: The aim is to investigate the changes of liver metastasis of mouse colon adenocarcinoma CT26 cell line by Poly (ADP-ribose) polymerase inhibition in vivo,and how it plays its role.Methods: 5-aminoisoquinolinone served as the inhibitor of PARP.The Balb/c mice syngenic colon adenocarcinoma CT26 cell line liver metastasis model was used. Various concentrations of 5-AIQ treated them by ip.. After 14 days, the changes of the spleen primary adenocarcinoma and liver metastasis carcinoma were observed in each group. Western blot was used to detect the PARP,NF-κBp65,ICAM-1,P-selectin,β1-integrins,MMP-2 and MMP-9 expressions of spleen primary adenocarcinoma .Results: 1.The carcinoma size of spleen in 5-AIQ treated groups was smaller than that in control group(5-AIQ-untreated group)(P<0.05).The numbers of liver metastatic nodule in 5-AIQ treated groups was less than that in control group(P<0.05); however, no statistical significance in the groups treated with different 5-AIQ dosages (P>0.05).2.The PARP ,NF-κBp65,ICAM-1,P-selectin,β1- integrins,MMP-2 and MMP-9 expressions of spleen primary carcinoma in 5-AIQ treated groups were lower significantly than that in control group(P<0.05).The correlation of PARP and NF-κBp65 was positive(P<0.05).The correlation of NF-κBp65 and ICAM-1,P-selectin,β1-integrins,MMP-2,MMP-9 was also positive(P<0.05).Conclusion:1. The growth and liver metastasis of mouse colon adenocarcinoma CT-26 cell were inhibited by PARP inhibitor 5-AIQ in vivo.2. The liver metastasis of mouse colorectal carcinoma CT26 cell line can be inhibited by PARP inhibitor is probably through inhibiting PARP ,then inhibiting NF-κB activity. As a result, it decrease the expression of nuclear factor-kappa dependent genes such as ICAM-1,P-selectin,β1-integrins,MMP-2,MMP-9 expressions. PARP may play an important role in the colon adenocarcinoma growth and metastasis.