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


CONCLUSIONS
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.
Zhang
Yiqun
Y
Department of General Surgery, Zhongshan Hospital of Fudan University, Shanghai 200032, China.
Qin
Xinyu
X
Zhang
Yanhong
Y
Zhao
Lili
L
Wang
Yigang
Y
Liu
Xinyuan
X
Yao
Liqing
L
D000256:Adenoviridae / Q000235:genetics*; D017501:Adenovirus E1B Proteins / Q000172:deficiency / Q000235:genetics; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D002470:Cell Survival; D002478:Cells, Cultured / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000235:genetics / Q000628:therapy* / Q000821:virology; D003131:Combined Modality Therapy; D004357:Drug Synergism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000821:virology; D005434:Flow Cytometry; D005472:Fluorouracil / Q000627:therapeutic use*; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050130:Oncolytic Virotherapy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics*; D015996:Survival Rate; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays
D017501:Adenovirus E1B Proteins; D000964:Antimetabolites, Antineoplastic; D012333:RNA, Messenger; D013482:Superoxide Dismutase; D005472:Fluorouracil