Combination of ZD55-MnSOD therapy with 5-FU enhances antitumor efficacy in colorectal cancer.

PURPOSE: ZD55-MnSOD is an E1B 55 kDa-deleted replication-competent adenovirus and armed with the therapeutic gene MnSOD. The expression of the therapeutic gene MnSOD increases with the selective replication of the oncolytic adenovirus (ZD55) so that ZD55-MnSOD has more significant activity than the replicate defective adenovirus Ad-MnSOD in vitro and in vivo. The tumor cannot be completely eradicated only with ZD55-MnSOD, although ZD55-MnSOD has obvious antitumor activity. 5-fluorouracil (5-FU) is still the most effective adjuvant therapy for patients with colorectal cancer.

METHODS: We reasoned that combined treatment of cancer cells with ZD55-MnSOD and 5-FU might have a synergistic effect. In vitro experiments with SW620 colorectal carcinoma cell line demonstrated that it was sensitive to ZD55-MnSOD, especially most sensitive to ZD55-MnSOD plus 5-FU treatment. Treatment with both ZD55-MnSOD and 5-FU could induce more significant apoptosis in cancer cells compared with ZD55-MnSOD or 5-FU alone, respectively. A better antitumor activity was observed by ZD55-MnSOD plus 5-fluorouracil (5-FU) treatment. Tumor growth was greatly inhibited by this combined treatment, and animal survival time increased.

CONCLUSION: These results show that, by using the combination therapies, a significant decrease in tumor mass can be achieved, which suggest that ZD55-MnSOD in combination with 5-FU may have potential clinical implications.