Abstract
This study aimed at investigating the anticancer potential of the recombinant adenovirus Ad-apoptin-hTERTp-E1a (Ad-VT) and its synergistic combination with paclitaxel (PTX) in breast cancer treatment. First, we used the Calcusyn software to analyze the synergy between the Ad-VT and paclitaxel, and to determine the final drug concentration. Second, we used crystal violet staining and WST-1 assays to analyze the inhibitory effect of Ad-VT and paclitaxel combination treatment on MCF-7, MDA-MB-231, and MCF-10A cells. Subsequently, we used Hoechst, Annexin V, JC-1 staining to analyze the inhibition pathway of drugs on breast cancer cells. We also used Transwell assays to analyze the cell migration and invasion of MCF-7 and MDA-MB-231 cells. The pGL4.51 plasmid was used to transfect and to generate MDA-MB-231 cells, that stably express luciferase (MDA-MB-231-LUC). The in vivo tumor inhibition effect of Ad-VT and paclitaxel combination treatment was subsequently confirmed using a tumor-bearing nude mouse model. This combination treatment can increase the inhibition of breast cancer cells and reduce paclitaxel toxicity. Ad-VT had a strong apoptosis-inducing effect on MCF-7 and MDA-MB-231 cells, that was mainly mediated through the mitochondrial apoptotic pathway. The combination of Ad-VT and paclitaxel could significantly increase the inhibition of breast cancer cell migration and invasion. Combination of Ad-VT and paclitaxel can inhibit tumor growth and reduce toxicity in vivo. Ad-VT can also inhibit the growth of breast cancer cells and promote their apoptosis. Meanwhile, when it is combined with paclitaxel, Ad-VT could play a significant role in a synergistic tumor inhibition.
Highlights
Cancer is one of the most important public health problems in the world
Cryopreserved human breast cancer cells MCF-7, MDA-MB231, and human normal mammary epithelial cells MCF-10A were purchased from the Cell Bank of the Shanghai Institute for Biological Science (Shanghai, China), and maintained in RPMI 1640 medium supplemented with 10% fetal bovine serum (FBS), 50 U/mL penicillin and 50 U/mL streptomycin, and incubated at 37◦C with 5% CO2
This effect was more significant with the combination treatment. These results indicate that the combination of Ad-VT and paclitaxel could induce apoptosis of breast cancer cells by activating the endogenous apoptotic pathway
Summary
Cancer is one of the most important public health problems in the world. Breast cancer is a serious threat to women’s health and its risk factors have been a hot topic. The most common treatment for breast cancer is surgery combined with radiotherapy and chemotherapy (Such as taxanes, anthracyclines, and cyclophosphamide, gemcitabine, cisplatin, etc.). Both methods are effective, they have significant side effects, preventing patients from obtaining high-quality life assurance. With developments in molecular biology, cell biology and virology, gene therapy has become an emerging mean of cancer treatment, in which Oncolytic virotherapy has shown great advantages, and is expected to be a reliable way to treat breast cancer
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