Enhanced anti-tumor activity by the combination of a conditionally replicating adenovirus mediated interleukin-24 and dacarbazine against melanoma cells via induction of apoptosis.
Malignant melanoma is one of the most lethal and aggressive human malignancies. It is notoriously resistant to all of the current therapeutic modalities, including chemotherapy. Suppressed apoptosis and extraordinary invasiveness are the distinctive features that contribute to the malignancy of melanoma. Dacarbazine (DTIC) has been considered as the gold standard for melanoma treatment with a response rate of 15-20%. Unfortunately, the resistance to this chemotherapeutic agent occurs frequently. ZD55-IL-24 is a selective conditionally replicating adenovirus that can mediate the expression of interleukin-24 (IL-24) gene, which has a strong anti-tumor effect. In this study, we hypothesized that a combination of ZD55-IL-24-mediated gene virotherapy and chemotherapy using DTIC would produce an increased cytotoxicity against human melanoma cells in comparison with these agents alone. Our results showed that the combination of ZD55-IL-24 and DTIC significantly enhanced the anti-tumor activity by more effectively inducing apoptosis in melanoma cells than either agent used alone without any overlapping toxicity against normal cells. This additive or synergistic effect of ZD55-IL-24 in combination with DTIC in killing human malignant melanoma cells implies a promising novel approach for melanoma therapy.
Jiang
Guan
G
Department of Dermatology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
Liu
Yan-Qun
YQ
Wei
Zhi-Ping
ZP
Pei
Dong-Sheng
DS
Mao
Li-Jun
LJ
Zheng
Jun-Nian
JN
D000256:Adenoviridae / Q000235:genetics / Q000502:physiology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000494:pharmacology*; D015536:Down-Regulation; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics*; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000628:therapy* / Q000821:virology; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D050130:Oncolytic Virotherapy / Q000379:methods*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D014161:Transduction, Genetic; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics; D051020:bcl-X Protein / Q000096:biosynthesis / Q000235:genetics; D000099180:Interleukin-24
D000970:Antineoplastic Agents; D003606:Dacarbazine; D007378:Interleukins; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D000099180:Interleukin-24; C494826:BAX protein, human; C494811:BCL2L1 protein, human