4.7 Article

Characterization of resistant MCF-7 breast cancer cells developed by repeated cycles of photodynamic therapy

期刊

FRONTIERS IN PHARMACOLOGY
卷 13, 期 -, 页码 -

出版社

FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2022.964141

关键词

breast cancer; photodynamic therapy; p-glycoprotein; MCF-7 cells; multidrug resistance

资金

  1. South African Research Chairs Initiative of the Department of Science and Technology
  2. National Research Foundation of South Africa
  3. South African Medical Research Council [98337]
  4. South African National Treasury [SAMRC EIP007/2021]

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Breast cancer is a severe global threat to health, and chemotherapy often faces the setback of tumor relapse and resistance. Photodynamic therapy shows promise as a treatment modality, but the emergence of resistant cell populations in breast cancer patients is a challenge. Studying resistant cells can provide insights into designing more effective treatment strategies.
Breast cancer mainly affects women and causes a severe global threat to health. It is often managed and treated with surgery, chemotherapy, immunotherapy, and radiation therapy. Generally, chemotherapy as a treatment option is often opposed by responsive tumor relapse and development of resistance, a significant setback of current treatment. Photodynamic therapy (PDT) offers a promising modality that can treat cancer by combining a photosensitizer and laser irradiation in the presence of oxygen. However, one problem of PDT in treating breast cancer is the apparition of the resistant cell population. Thus, we aimed for stepwise selection and characterization of MCF-7 cells resistant to PDT with a sulfonated zinc phthalocyanine (ZnPcS4) photosensitizer. The wild-type MCF-7 was exposed to successive cycles of ZnPcS4-PDT, and 10resistant populations were finally obtained. In wild-type and parental cells, we analyzed the cell morphology (light microscopy), cell cycle (BrdU staining), cell viability (MTT assay), antioxidant activity (superoxide dismutase measurement), and immunofluorescence expression of resistant p-glycoprotein (P-gp). The results indicate that resistant cells showed a mesenchymal cell phenotype, few differences in antioxidant activity, an increased DNA synthesis, and more expression of P-gp than the wild-type parental cells. These distinctive features of resistant cells can provide insight into the emergence of MCF-7 cell resistance to PDT, which was necessary to design the best therapeutic procedure for improved efficacy.

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