Metformin pretreatment reduces effect to dacarbazine and suppresses melanoma cell resistance

Area of Science:

• Oncology
• Cell Biology
• Biochemistry

Background:

• Dacarbazine (DTIC) resistance in B16F10 melanoma cells is a significant clinical challenge.
• Oxidative stress plays a crucial role in the development of drug resistance.
• Understanding the interplay between metformin, DTIC, and oxidative stress is vital for improving melanoma treatment.

Purpose of the Study:

• To investigate the role of oxidative stress in DTIC resistance in B16F10 melanoma cells.
• To determine the effect of metformin on DTIC resistance and associated oxidative stress markers.
• To explore the dual role of metformin in modulating DTIC resistance.

Main Methods:

• Induction of DTIC resistance in B16F10 murine melanoma cells.
• Administration of metformin before and during DTIC resistance induction (MET-DTIC).
• Analysis of oxidative stress biomarkers including malondialdehyde (MDA), thiols, p53, 8-hydroxy-2'-deoxyguanosine (8-OH-DG), nuclear factor kappa B (NF-ĸB), and Nrf2.

Main Results:

• DTIC-resistant cells (DTIC-res) exhibited increased MDA and thiols, with reduced nuclear p53, 8-OH-DG, NF-ĸB, and Nrf2.
• Metformin co-administration (MET-DTIC) weakened the DTIC-resistant phenotype by increasing antioxidant thiols, MDA, nuclear p53, 8-OH-DG, Nrf2, and reducing NF-ĸB.
• Exclusive metformin administration (MET) also induced DTIC resistance, showing increased thiols, MDA, and reduced nuclear p53, 8-OH-DG, NF-ĸB, and Nrf2 compared to control.

Conclusions:

• Oxidative stress and specific biomarkers are implicated in DTIC resistance in B16F10 cells.
• Metformin exhibits a dual role, capable of either preventing or inducing DTIC resistance depending on the experimental context.
• These findings provide insights for future research into overcoming DTIC resistance in melanoma.