Abstract
Malignant melanoma is one of the most lethal and aggressive human malignancies. Suppressed apoptosis and extraordinary invasiveness are the distinctive features that contribute to malignant melanoma. The alkylating agent temozolomide (TMZ) is one of the most effective single chemotherapeutic agents for patients with malignant melanoma, but resistance develops quickly and with high frequency. We constructed a dual-regulated oncolytic adenovirus expressing interleukin 24 (IL-24) gene (Ki67-ZD55-IL-24) by utilizing the Ki67 promoter to replace the native viral promoter of E1A gene. We investigated whether a combination of Ki67-ZD55-IL-24-mediated gene virotherapy and chemotherapy using TMZ produces increased cytotoxicity against human melanoma cells via the induction of apoptosis. Our data indicate that this novel strategy thus holds promising potentials for further developing an effective approach to treat malignant melanoma.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenoviridae / genetics*
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Antineoplastic Agents, Alkylating / pharmacology*
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Apoptosis*
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Blotting, Western
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Cell Cycle
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Cell Proliferation
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Combined Modality Therapy
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DNA Modification Methylases / metabolism
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DNA Repair Enzymes / metabolism
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Dacarbazine / analogs & derivatives*
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Dacarbazine / pharmacology
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Genetic Therapy
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Genetic Vectors
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Humans
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Immunoenzyme Techniques
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Interleukins / genetics*
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Ki-67 Antigen / genetics
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Melanoma / genetics
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Melanoma / pathology
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Melanoma / therapy*
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Melanoma / virology
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Oncolytic Virotherapy*
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Temozolomide
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Tumor Cells, Cultured
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Tumor Suppressor Protein p53 / metabolism
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Tumor Suppressor Proteins / metabolism
Substances
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Antineoplastic Agents, Alkylating
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Interleukins
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Ki-67 Antigen
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TP53 protein, human
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Tumor Suppressor Protein p53
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Tumor Suppressor Proteins
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interleukin-24
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Dacarbazine
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DNA Modification Methylases
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MGMT protein, human
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DNA Repair Enzymes
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Temozolomide