title: 5/35 fiber-modified conditionally replicative adenovirus armed with p53 shows increased tumor-suppressing capacity to breast cancer cells.
abstract: Conditionally replicative adenoviruses (CRAds) are widely used for cancer biotherapy and show a significant growth-suppressing effect on many types of cancer. However, it was reported that breast cancer was highly resistant to the infection of traditionally used adenovirus of serotype 5 (Ad5)-based CRAds. Although partial substitution of the fiber protein of replication-deficient Ad5 with that of adenovirus of serotype 35 (Ad35) facilitated infection of breast cancer cells by adenoviral vectors, it is still unknown whether this modification can improve CRAds in their tumor-eliminating capacity. We generated a 5/35 fiber-modified CRAd with a p53 cDNA construct and investigated whether this alteration in fiber region can make CRAds suppress the growth of breast cancer more effectively. Our data reinforced the proposal that 5/35-modified fiber conferred higher adenovirus infectivity for breast cancer cells than natural Ad5 fiber. Interestingly, 5/35 fiber-modified CRAd replicated more efficiently in breast cancer cells than Ad5-based CRAd. We also found 5/35 fiber-modified CRAd mediated higher expression of p53 in breast cancer cells. In vitro, 5/35 fiber-modified CRAd eliminated breast cancer cells more efficiently. Growth of xenograft tumors in nude mice was also significantly retarded by 5/35 fiber-modified CRAd. The 5/35 fiber-modified CRAd suppressed the growth of breast cancer cells more effectively than Ad5-based CRAd, both in vitro and in vivo. Thus CRAd with 5/35 hybrid fiber may be a promising vector for breast cancer treatment.
authors.affiliation: Laboratory of Gene and Viral Therapy, Eastern Hepatobiliary Surgical Hospital, The Second Military Medical University, Shanghai 200438, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: He
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Chunyan
authors.initials: C
authors.lastname: Yang
authors.forename: Changqing
authors.initials: C
authors.lastname: Su
authors.forename: Chengliang
authors.initials: C
authors.lastname: Zhou
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Linfang
authors.initials: L
authors.lastname: Li
authors.forename: Hongping
authors.initials: H
authors.lastname: Wu
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Liu
authors.forename: Mengchao
authors.initials: M
authors.lastname: Wu
authors.forename: Qijun
authors.initials: Q
authors.lastname: Qian
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001943:Breast Neoplasms / Q000503:physiopathology* / Q000628:therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D051916:Membrane Cofactor Protein / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050130:Oncolytic Virotherapy; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology; D023041:Xenograft Model Antitumor Assays
chemical_list: D051916:Membrane Cofactor Protein; D011991:Receptors, Virus; D016159:Tumor Suppressor Protein p53; C085301:adenovirus receptor