“… 6–11 Among them, the emergence of oncolytic adenovirus therapy has dramatically reduced the side effects of chemotherapy. 12 …”
Section: Introductionmentioning
confidence: 99%
“…[6][7][8][9][10][11] Among them, the emergence of oncolytic adenovirus therapy has dramatically reduced the side effects of chemotherapy. 12 Apoptin is a small protein consisting of 121 amino acids that was first isolated and identified from the chicken anemia virus (CAV) in Japan in 1974 and is encoded by the VP3 gene of CAV. [13][14][15][16] Phosphorylated apoptin is located in the nucleus of tumor cells and the cytoplasm of normal cells, and apoptin can only cause cell death when it is located in the nucleus.…”
Purpose
Oncolytic virus therapy has gradually become an integral approach in cancer treatment. We explored the therapeutic effects of the combination of a dual cancer-selective anti-tumor recombinant adenovirus (Ad-Apoptin-hTERTp-E1a) and cyclophosphamide on breast cancer cells.
Methods
The inhibition of MCF-7 and MDA-MB-231 breast cancer cells by Ad-Apoptin-hTERTp-E1a (Ad-VT), cyclophosphamide, and Ad-VT + Cyclophosphamide was investigated using the CCK-8 assay. The combination index (CI) was calculated using CalcuSyn software to determine the best combination based on the inhibition rates of the different treatment combinations. The CCK-8 assay and crystal violet staining were used to detect the cytotoxicity of the combined Ad-VT and cyclophosphamide in breast cancer cells and breast epithelial cells. Subsequently, Hoechst staining, annexin V flow cytometry, and JC-1 staining were used to analyze the inhibitory pathway of Ad-VT plus cyclophosphamide on breast cancer cells. Cell migration and invasion of breast cancer cells were assessed using the cell-scratch and Transwell assays. The anti-tumor effects of different treatment groups in a tumor-bearing nude mouse model also were analyzed.
Results
The treatment combination of Ad-VT (40 MOI) and cyclophosphamide (400 µM) significantly inhibited MCF-7 and MDA-MB-231 cells and reduced the toxicity of cyclophosphamide in normal cells. Ad-VT primarily induced breast cancer cell apoptosis through the endogenous apoptotic pathway. Apoptosis was significantly increased after treatment with Ad-VT plus cyclophosphamide. The combination significantly inhibited the migration and invasion of MCF-7 and MDA-MB-231 cells. The in vivo experiments demonstrated that exposure to Ad-VT plus cyclophosphamide significantly inhibited tumor growth and extended the survival time of the nude mice.
Conclusion
Ad-VT plus cyclophosphamide reduced toxicity and exhibited increased efficacy in treating breast cancer cells.
“… 6–11 Among them, the emergence of oncolytic adenovirus therapy has dramatically reduced the side effects of chemotherapy. 12 …”
Section: Introductionmentioning
confidence: 99%
“…[6][7][8][9][10][11] Among them, the emergence of oncolytic adenovirus therapy has dramatically reduced the side effects of chemotherapy. 12 Apoptin is a small protein consisting of 121 amino acids that was first isolated and identified from the chicken anemia virus (CAV) in Japan in 1974 and is encoded by the VP3 gene of CAV. [13][14][15][16] Phosphorylated apoptin is located in the nucleus of tumor cells and the cytoplasm of normal cells, and apoptin can only cause cell death when it is located in the nucleus.…”
Purpose
Oncolytic virus therapy has gradually become an integral approach in cancer treatment. We explored the therapeutic effects of the combination of a dual cancer-selective anti-tumor recombinant adenovirus (Ad-Apoptin-hTERTp-E1a) and cyclophosphamide on breast cancer cells.
Methods
The inhibition of MCF-7 and MDA-MB-231 breast cancer cells by Ad-Apoptin-hTERTp-E1a (Ad-VT), cyclophosphamide, and Ad-VT + Cyclophosphamide was investigated using the CCK-8 assay. The combination index (CI) was calculated using CalcuSyn software to determine the best combination based on the inhibition rates of the different treatment combinations. The CCK-8 assay and crystal violet staining were used to detect the cytotoxicity of the combined Ad-VT and cyclophosphamide in breast cancer cells and breast epithelial cells. Subsequently, Hoechst staining, annexin V flow cytometry, and JC-1 staining were used to analyze the inhibitory pathway of Ad-VT plus cyclophosphamide on breast cancer cells. Cell migration and invasion of breast cancer cells were assessed using the cell-scratch and Transwell assays. The anti-tumor effects of different treatment groups in a tumor-bearing nude mouse model also were analyzed.
Results
The treatment combination of Ad-VT (40 MOI) and cyclophosphamide (400 µM) significantly inhibited MCF-7 and MDA-MB-231 cells and reduced the toxicity of cyclophosphamide in normal cells. Ad-VT primarily induced breast cancer cell apoptosis through the endogenous apoptotic pathway. Apoptosis was significantly increased after treatment with Ad-VT plus cyclophosphamide. The combination significantly inhibited the migration and invasion of MCF-7 and MDA-MB-231 cells. The in vivo experiments demonstrated that exposure to Ad-VT plus cyclophosphamide significantly inhibited tumor growth and extended the survival time of the nude mice.
Conclusion
Ad-VT plus cyclophosphamide reduced toxicity and exhibited increased efficacy in treating breast cancer cells.
“…The emergence of oncolytic adenoviral therapy has led to a significant reduction in the side effects of chemotherapy. 4 …”
Section: Introductionmentioning
confidence: 99%
“…At present, the most common treatment for breast cancer is still the combination of surgical treatment and chemotherapy 4,5 . Doxorubicin is the main chemotherapy drug in clinical treatment of breast cancer.…”
Section: Introductionmentioning
confidence: 99%
“…Viral therapy can be divided into two main types: (1) the use of non‐replicating viruses as vectors for tumour gene therapy and (2) the use of replicating viruses as oncolytic agents. The emergence of oncolytic adenoviral therapy has led to a significant reduction in the side effects of chemotherapy 4 …”
In this study, we compared the inhibitory effects of recombinant oncolytic adenovirus (Ad‐apoptin‐hTERTp‐E1a, Ad‐VT) with that of doxorubicin (DOX), a first‐line chemotherapy drug, and tamoxifen (TAM), an endocrine therapy drug, on the proliferation of breast cancer cells. We found that Ad‐VT could effectively inhibit the proliferation of breast cancer cells (
p
< 0.01); the inhibition rate of Ad‐VT on normal mammary epithelial MCF‐10A cells was less than 20%. DOX can effectively inhibit the proliferation of breast cancer cells and also has a strong inhibitory effect on MCF‐10A cells (
p
< 0.01). TAM also has a strong inhibitory effect on breast cancer cells, among which the oestrogen‐dependent MCF‐7 cell inhibition was stronger (
p
< 0.01), At higher concentrations, TAM also had a high rate of inhibition (>70%) on the proliferation of MCF‐10A cells. We also found that both recombinant adenovirus and both drugs could successfully induce tumour cell apoptosis. Further Western blot results showed that the recombinant adenovirus killed breast cancer cells through the endogenous apoptotic pathway. Analysis of the nude mouse subcutaneous breast cancer model showed that Ad‐VT significantly inhibited tumour growth (the luminescence rate of cancer cells was reduced by more than 90%) and improved the survival rate of tumour‐bearing mice (
p
< 0.01). Compared with DOX and TAM, Ad‐VT has a significant inhibitory effect on breast cancer cells, but almost no inhibitory effect on normal breast epithelial cells, and this inhibitory effect is mainly through the endogenous apoptotic pathway. These results indicate that Ad‐VT has significant potential as a drug for the treatment of breast cancer.
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