A Study Of Oncolytic Adenovirus KH901 Enhancing The Killing Efficacy Of 5-Fu

Part 1As a conditionally-replicating adenovirus, KH901 could selectively replicate in a series of cancer cells, and played a significant killing efficacy. Thus we investigated the effects of KH901 on LoVo cells, and the possible combined effects of KH901 with additional 5-Fu. Cytotoxicity assays were used to determine the toxic effects of KH901 and 5-Fu along or the combination of the two agents on LoVo cells. KH901 showed a dose dependent killing efficacy on LoVo cells, KH901 and 5-Fu played a synergistic effect in killing LoVo cells, the IC50 value of KH901 and 5-Fu are 6pfu and 9.84E-6M/L respectively. KH901 has significant potential as an oncolytic virus and could play a synergistic effect with 5-fu, our results is very beneficial for clinical trials.Part 2A preliminary research of Oncolytic adenovirus KH901 increasingthe killing efficacy of 5-Fu on colorectal cancer LoVo cellsOncolytic adenovirus played a synergistic effect with 5-Fu, and the combination of the two agents could significantly promote the killing efficacy on LoVo cells. In order to explore the mechanism of the synergistic effect, we use Flow Cytometry to assay the cell cycles of the LoVo cells after treated with KH901 and 5-Fu along or the combination of the two agents. Results showed that KH901 along or combined with 5-Fu could facilitate the cells to enter S-phase and at the same time decrease G2/M phase cells. Thus it could be concluded that the synergistic effect is due to the increase of S-phase cells and decrease of G2/M phase cells treated with KH901 plus 5-Fu, since 5-Fu is a S-phase specific anticancer agent.