Wortmannin as targeted therapeutic agent for the treatment of Triple-Negative breast cancer

Abstract

Purpose: To investigate the inhibitory effect of wortmannin on inhibition of BT-20 and BT-474 breast cancer cells in Athymic nu/nu mice model. Methods: Forty Athymic nu/nu mice were randomly assigned to 4 groups of 10 each, namely, BT-20 control, BT-20 treatment, BT-474 control and BT-474 treatment groups. The mice were injected with 2.5 × 105 BT-20 and BT-474 cells under anesthesia. Those in the treatment groups were given wortmannin (7 mg/kg) in DMSO daily intraperitoneally whereas the animals in control groups received an equal volume of DMSO for 21 days after the cancer attained palpable stage. Western blot analysis was carried out using enhanced chemiluminescence reagent while Protean IEF cell unit was used for 1-D electrophoresis. Results: The results showed a significant decrease in the growth of the tested cancer cell lines on treatment with wortmannin at 7 mg/kg daily for 21 days. The volume of tumor in the treatment group was reduced to 42.72 ± 9.45 compared to 79.43 ± 17.11 mm3 in the control group after 21 days treatment (p < 0.005). It also changed the expression of microRNA in BT-20 cells. Exposure of BT-20 cells to wortmannin for 24 h resulted in the altered expression of proteomes. Wortmannin treatment increased the expression of miRs including miR 19a/b, 22, 29b/c, 181c/d, 195 and 663. Western blot data showed increase in the expression of NME1 (NM23 H1) and reduction in the expression of vimentin after treatment with wortmannin. Conclusion: Wortmannin can be of benefit in the treatment of human breast cancer.