Vitamin D Modulates the Response of Patient-Derived Metastatic Melanoma Cells to Anticancer Drugs

Area of Science:

• Oncology
• Dermatology
• Molecular Biology

Background:

• Melanoma is a lethal, treatment-resistant skin cancer with high recurrence rates.
• Previous research indicated that 1,25(OH)2D3 potentiates dacarbazine and cediranib efficacy.
• Patient-derived melanoma cultures were established as a preclinical model.

Purpose of the Study:

• To investigate the efficacy of 1,25(OH)2D3 as an adjuvant in melanoma treatment.
• To evaluate the combined effects of 1,25(OH)2D3 with cediranib or vemurafenib on patient-derived melanoma cells.
• To explore the role of mitochondrial bioenergetics and cancer-associated fibroblasts in melanoma response.

Main Methods:

• Established and characterized patient-derived melanoma cultures.
• Preconditioned cells with 1,25(OH)2D3, then treated with cediranib or vemurafenib based on BRAF mutation status.
• Assessed cell growth, motility, and mitochondrial respiration.
• Observed the influence of cancer-derived fibroblasts (CAFs) over time.

Main Results:

• 1,25(OH)2D3 preconditioning significantly enhanced inhibition of melanoma cell growth and motility compared to cediranib monotherapy.
• Mitochondrial respiration parameters (oxygen consumption, basal respiration, ATP-linked respiration) were significantly decreased.
• 1,25(OH)2D3 also reduced viability and mobility of BRAF+ cells treated with vemurafenib.
• Cancer-derived fibroblasts became the dominant cell fraction, suggesting melanoma growth dependency.

Conclusions:

• 1,25(OH)2D3 preconditioning enhances cediranib efficacy, likely through modulating mitochondrial bioenergetics.
• The active form of vitamin D shows potential as an adjuvant therapy for malignant melanoma.
• Melanoma growth may be dependent on cancer-associated fibroblasts.