Adenovirus carrying TIMP-3: a potential tool for cervical cancer treatment.
OBJECTIVE
Previous studies have demonstrated the pivotal roles of matrix metalloproteinases (MMPs) in cervical cancer progression. Tissue inhibitor of metalloproteinases-3 (TIMP-3) can inhibit all of MMPs, and its overexpression can retard many kinds of tumor growth. Especially, a potent bystander effect would make it to be more advisable for treating cervical cancer whose primary growth pattern is to invade adjacent structures. These characters prompted the authors to explore its further applicability in human cervical cancer.


METHODS
We constructed a replication deficient adenoviral vector carrying TIMP-3 (Ad-TIMP-3). It was transferred into different cervical cancer cell lines in vitro and was injected into the tumor xenografts of nude mice in vivo.


RESULTS
Overexpression of TIMP-3 by adenovirus vector arrested cervical cancer cells in G2/M phase. It also promoted growth inhibition of cancer cells by bystander effects. Ad-TIMP-3 infection produced a more potent cell killing effect than Ad-p53 (P<0.05). A synergic effect was observed when Ad-TIMP-3 and cisplatin (cDDP) were used in combination (D<1). In vivo, Ad-TIMP-3 could inhibit cervical cancer xenografts growth. Compared with Ad-TIMP-3 and cDDP groups, tumor growth in Ad-TIMP-3 combined with cDDP group was inhibited more significantly (P<0.05).


CONCLUSIONS
These findings indicated that Ad-TIMP-3 bear a therapeutic potential for cervical cancer.
Zhang
Ying
Y
Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, No.1 Shuaifuyuan, Dong Dan District, Beijing 100007, PR China.
Qian
Haili
H
Lin
Chen
C
Lang
Jinghe
J
Xiang
Yang
Y
Fu
Ming
M
Zhang
Xueyan
X
Liang
Xiao
X
D000256:Adenoviridae / Q000235:genetics; D000258:Adenovirus Infections, Human / Q000235:genetics / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology; D003131:Combined Modality Therapy; D005260:Female; D016195:G2 Phase / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000096:biosynthesis / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy* / Q000821:virology; D023041:Xenograft Model Antitumor Assays
C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3; D002945:Cisplatin