This work is to investigate the combined tumor-suppression effect of Adenovirus-mediated human ING4 (Ad-hING4) and 125I seed on human pancreatic cancer xenograft and the possible mechanisms.Ad-hING4 recombinant adenovirus vector was transected into QBI-293A cells and high titre adenovirus was obtained.Subcutaneous tumor models were established with 25 nude mice with human pancreatic cancer cell line PANC-1.They were randomly divided into 5 groups: PBS control group

Ad carrier group

125I seed brachytherapy group

Ad-hING4 gene treatment group

combined 125I seed and Ad-hING4 group.The tumor volumes were measured every 5 days after treatment

and were sacrificed on the 20th day.The tumors were measured and weighed to determine the ratio of tumor-suppression and Jin-Shi q value.Morphological changes of tumor cells

the tissue injury and apoptotic index AI were examined on pathological sections.MVD

Survivin and Caspase3 were tested in immunohistochemistry.The results show that the tumor-suppressive ratio of the 125I seed group

Ad-hING4 group

combined treatment group were

respectively

34.19%(P < 0.01)

31.50%(P < 0.01)

and 67.15% (P < 0.01) which was markedly higher than other two groups (P < 0.01).The pathological examination found degenerative necrosis at the site was nearby the seed but the living tumor cell still presented faraway from the seed.AI and Caspase3 positive cells in the treatment groups were higher than PBS group significantly (P < 0.05)

and the combined treatment group was higher than other two treatment groups significantly (P < 0.01).MVD and Survivin positive cells in the treatment groups were lower than PBS group significantly (P < 0.05)

and the combined treatment group was lower than other 2 treatment groups significantly (P < 0.01)

too.There was no significant difference between Ad group and PBS group in every detection index (P > 0.05).It can be concluded that 125I seed and Ad-hING4 inhibit the growth of PANC-1 pancreatic cancer on nude mice significantly.These indicate a synergy of the combined treatments in tumor-suppression and Ad-hING4 is a promising novel radiosensitizer.The mechanisms of tumor-suppressive may be multi-pathways such as down-regulation the expression of Survivin and up-regulation the expression of Caspase3 to induce apoptosis and inhibit angiogenesis.