Medicarpin reduces cisplatin resistance and causes apoptosis by inhibiting the AKT/Bcl2 pathway in breast cancer

Medicarpin (Med) is a natural flavonoid extract that has demonstrated promising anti-tumor activity in a variety of cancers. The effect of Med on malignant progression and chemotherapy resistance in breast Cancer (BC) is currently unclear. Cisplatin-resistant (CisR) MCF-7 cells were constructed. The effects of different doses of Med and Cisplatin (Cis) on the viability of MCF-7 and CisR-MCF-7 cells were examined through Cell Counting Kit-8 (CCK-8) assay. Biological characterization of BC cells was evaluated by EdU staining, Hoechst 33,258 staining, Transwell assay, flow cytometry, and Scratch-wound assay. Comet assay and immunofluorescence to assess cellular DNA damage. Western blot detected DNA damage-related proteins, apoptosis-related protein, cycle-blocking-related protein, and Akt/Bcl2 pathway protein levels. Additionally, a nude mice subcutaneous graft tumor model was constructed, and the impact of Med on tumor growth was explored by pathological staining. The results showed that Med (80 μM) decreased the viability of both MCF-7 and CisR-MCF-7 cells. Either Med or Cis suppressed cell proliferation, hindered migration and invasion, induced Apoptosis, and caused cellular DNA damage and cycle arrest. Med blocked the Akt/Bcl2 pathway. All of the above indices were significantly reversed in BC cells after addition of the Akt Agonist SC79. However, the Akt Inhibitor MK2206 increased the effect of Med, further inhibited the malignant progression of BC cells, and induced cellular DNA damage and cycle arrest. In addition, injection of either Med or Cis caused a decline in Ki67 positivity and a rise in TUNEL positivity in tumor tissues, which in turn suppressed tumor growth. The effect of the combined treatment of the two was higher than single treatment, indicating that Med could improve the therapeutic efficacy of Cis and reduce the drug resistance of CisR-MCF-7 cells. Med inhibits BC malignant biological behavior and reduces Cis resistance by blocking the Akt/Bcl2 pathway.

Breast cancer; Cisplatin-resistant; Cycle arrest; DNA damage; Medicarpin.