Temozolomide (TMZ) is widely used to treat melanoma; however, response rates to TMZ are low because of rapid and frequent resistance.,Conditionally, replicative adenoviruses (CRAds) are an effective and promising approach.,The receptor for adenovirus is coxsackie‐adenovirus receptor (CAR), which is poorly expressed in most cells.,However, CD46, which is the receptor of species B adenoviruses (Ads), is highly expressed in many cells.,We constructed CRAd F5/35‐ZD55‐IL‐24, which uses the viral receptors CAR and CD46 for entry into cells.,We investigated the antitumor effect of F5/35‐ZD55‐IL‐24 in combination with TMZ to treat melanoma in vitro and in vivo.,The \results indicated that F5/35‐ZD55‐IL‐24 in combination with TMZ produced additive or synergistic antitumor and pro‐apoptotic effects in melanoma cells.,The combination of F5/35‐ZD55‐IL‐24 and TMZ significantly inhibited the growth of melanoma in vivo.,In addition, the antitumor effect of F5/35‐ZD55‐IL‐24 was superior to that of ZD55‐IL‐24 and ZD55‐IL‐24 combined with TMZ.,The use of F5/35‐ZD55‐IL‐24 in conjunction with TMZ is a promising approach for anti‐melanoma therapy.,Our results indicated that F5/35‐ZD55‐IL‐24 in combination with TMZ produced additive or synergistic antitumor effect and pro‐apoptotic effect in melanoma cells highly expressed CD46.,The combination of F5/35‐ZD55‐IL‐24 and TMZ significantly inhibited the growth of melanoma in vivo.,We also found the antitumor effect of F5/35‐ZD55‐IL‐24 was superior to ZD55‐IL‐24, the combination of F5/35‐ZD55‐IL‐24 and TMZ had a more significant antitumor effect than ZD55‐IL‐24 combining with TMZ.
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.,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.,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.,This strategy holds promising potential for the further development of an effective approach to treat malignant melanoma.