ZD55-Sur-EGFP Suppresses The Growth Of Colon Carcinoma And Synergistically Inhibits Its Lymphatic Metastasis With 5-FU

RESEARCH 1 ZD55-SUR-EGFP SUPPRESSES HUMAN COLON CARCINOMA GROWTH IN VITRO AND IN VIVOObjectiveTo investigate the effects of oncolytic adenovirus armed with Survivin shRNA on the growth, replication and apoptosis of colorectal cancer (CRC) cells and its therapeutic effects on xenograft model.MethodOncolytic adenovirus carrying a Survivin shRNA (ZD55-Sur-EGFP) was used to transfect human colorectal cancer cell lines SW480,LoVo and normal cell line Intestinal Epithelial Cell (IEC) , ZD55-EGFP, Ad-Sur-EGFP and Ad-EGFP were used as controls. We examined the expressions of Survivin mRNA and protein by RT-PCR and Western Blot, the inhibition effect of viruses on cells by MTT cell viability assay, CPE assay and FCM.The in vivo study was performed on nude mice subcutaneous xenograft model by virus injection through the tail vein. The inhibitory effects were evaluated by tumor size and Survivin protein expression.ResultIn the in vitro study, ZD55-Sur-EGFP could significantly suppress the Survivin expression (P< 0.0001)and cell viability (P< 0.05)compared with ZD55-EGFP, Ad-Sur-EGFP and Ad-EGFP, and the apoptosis population in ZD55-Sur-EGFP group was obviously increased(P< 0.05). Similar results were acquired in the in vivo study. ZD55-Sur-EGFP significantly attenuated Survivin expression and tumor growth (P< 0.05).ConclusionWe concluded ZD55-Sur-EGFP may be a promising therapy for CRC.RESEARCH 2 ZD55-SUR-EGFP AND 5-FLUOROURACIL SYNERGISTICALLY SUPPRESS THE LYMPHATIC METASTASIS OF COLON CARCINOMAObjectiveTo investigate the synergistic effects of ZD55-Sur-EGFP and 5-FU on Survivin expression, replication and invasion of colorectal cancer cells and their therapeutic potential on foot pad xenograft model.MethodZD55-Sur-EGFP and 5-FU were used alone or in combination in SW480 and LoVo cells to examine the expression of Survivin protein by Western Blot, the inhibition of cell proliferation was accessed by MTT cell viability assay, the migration and invasion was analyzed by transwell assay.The in vivo study was performed on nude mice foot pad xenograft model. The inhibitory effects were evaluated by tumor size and sentinel lymph nodes with metastasis.Result5-FU did not add to the inhibition of Survivin protein expression by Western Blot, ZD55-Sur-EGFP and 5-FU in combination could significantly suppress the cell viability compared to single agent(P<0.05), and administration of both ZD55-Sur-EGFP and 5-FU inhibit the migration and invasion of colorectal cancer cell lines(P<0.05). Similar results were acquired in the in vivo study. When ZD55-Sur-EGFP was combined with 5-FU, the metastases to sentinel lymph nodes were obviously suppressed(P<0.05).ConclusionThe combination of ZD55-Sur-EGFP and 5-FU could attenuate tumor cell growth, migration and invasion in vitro, and also decrease lymphatic metastasis of colorectal cancer cells in vivo, may be a promise therapy for CRC with lymphatic metastasis.