Potent anti-tumour activity of a novel conditionally replicating adenovirus for melanoma via inhibition of migration and invasion.
BACKGROUND
Conditionally replicating adenoviruses (CRAds) represent a novel class of oncological therapeutic agents. One strategy to ensure tumour targeting is to place the essential viral genes under the control of tumour-specific promoters. Ki67 has been selected as a cancer gene therapy target, as it is expressed in most malignant cells but is barely detectable in most normal cells. This study aimed to investigate the effects of a Ki67 promoter-controlled CRAd (Ki67-ZD55-IL-24) on the proliferation and apoptosis of melanoma cells.


METHODS
Melanoma cells were independently treated with Ki67-ZD55-IL-24, ZD55-IL-24, Ki67-ZD55, and ZD55-EGFP. The cytotoxic potential of each treatment was assessed using cell viability measurements. Cell migration and invasion were assayed using cell migration and invasion assays. Apoptosis was assayed using the annexin V-FITC assay, western blotting, reverse transcriptase PCR (RT-PCR), haematoxylin and eosin (H&E) staining, and the TUNEL assay.


RESULTS
Our results showed that Ki67-ZD55-IL-24 had significantly enhanced anti-tumour activity as it more effectively induced apoptosis in melanoma cells than the other agents. Ki67-ZD55-IL-24 also caused the most significant inhibition of cell migration and invasion of melanoma cells. Furthermore, apoptosis was induced more effectively in melanoma xenografts in nude mice.


CONCLUSIONS
This strategy holds promising potential for the further development of an effective approach to treat malignant melanoma.
Department of Dermatology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.
G
G
Jiang
Department of Dermatology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China.
C-S
CS
Yang
Department of Dermatology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China.
D
D
Xu
Department of Dermatology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China.
C
C
Sun
Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China.
J-N
JN
Zheng
Department of Dermatology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.
T-C
TC
Lei
Department of Dermatology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China.
Y-Q
YQ
Liu
D000256:Adenoviridae / Q000235:genetics / Q000502:physiology*; D017501:Adenovirus E1B Proteins / Q000172:deficiency / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D045744:Cell Line, Tumor; D002465:Cell Movement; D003673:Defective Viruses / Q000235:genetics / Q000502:physiology*; D015967:Gene Expression Regulation, Viral; D005813:Genes, Synthetic; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000502:physiology; D019394:Ki-67 Antigen / Q000235:genetics; D008297:Male; D008545:Melanoma / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D050130:Oncolytic Virotherapy; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins; D014779:Virus Replication / Q000235:genetics; D023041:Xenograft Model Antitumor Assays; D000099180:Interleukin-24
D017501:Adenovirus E1B Proteins; D007378:Interleukins; D019394:Ki-67 Antigen; D011993:Recombinant Fusion Proteins; D000099180:Interleukin-24