Selective replication of miR-145-regulated oncolytic adenovirus in MCF-7 breast cancer cells

Abstract

Aim: Selective replication of oncolytic viruses in cancer cells is a challenge in virotherapy. miRNA-145 is downregulated in breast cancer cell lines and cancer tissues. In order to target replication of the oncolytic adenovirus 5 in breast cancer cells, we constructed a miRNA-145-regulated oncolytic adenovirus (AD5-miR-145-5pT) by inserting five copies of the miR-145-5p target sites into the 3'-untranslated region of E1A gene. Materials & methods: The MCF-7 human breast cancer cell line and the normal human mammary epithelial cells (HMEpC) were infected with AD5-miR145-5pT, and then the viral titers were measured 12, 24, 36 and 48 h postinfection using TCID50 assay. Results: Growth kinetic analysis of AD5-miR-145-5pT in MCF-7 cells and HMEpC showed that replication of the engineered adenovirus was inhibited in HMEpC as normal breast cells, whereas the virus efficiently replicated in MCF-7 cells. Infectious titer of AD5-miR-145-5pT at 48 h postinfection in HMEpC was 3.2 log TCID50 lower than that of the AD5-control. Conclusion: These results suggest that AD5-miR-145-5pT may be a feasible approach for the targeting of breast cancer cells and other cancers where the miRNA-145 is downregulated. miR-145-5p can be applied to miR-targeting of other oncolytic viruses toward breast carcinoma cells.