Analysis of dacarbazine resistance in melanoma mediated by abcb1 overexpression and its reversal through targeted inhibition

LIAO Yilong; DENG Yuanxiong

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Journal of Hunan Normal University(Medical Science) ›› 2025, Vol. 22 ›› Issue (3) : 8-14.

Analysis of dacarbazine resistance in melanoma mediated by abcb1 overexpression and its reversal through targeted inhibition

LIAO Yilong, DENG Yuanxiong

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Abstract

Objective The aim of this study was to explore the resistance of dacarbazine in melanoma A375 cells driven by the high expression of ABCB1 gene and its targeted reversal strategy through the construction of melanoma drug-resistant cell lines. Methods A375 melanoma dacarbazine resistant cell line (A375-DacR) was constructed by gradually increasing Dacarbazine concentration and long-term induction of melanoma A375 cells. CCK-8 assay and flow cytometry were used to evaluate the drug resistance level of drug-resistant cell lines. The expression levels of ABCB1 gene and its coding protein P-gp in A375 cells and A375-DACR cells were detected by qPCR and Western Blot. The cell cycle distribution was detected by flow cytometry. Dacarbazine resistant cell lines were treated with ABCB1-targeted inhibitors to evaluate the effect of resistance reversal. Results The dacarbazine-resistant A375 melanoma cell line (A375-DacR) was successfully constructed with a resistance index greater than 5. The mRNA and protein expression levels of ABCB1 in A375-DacR cells were significantly upregulated, highlighting its pivotal role in the development of drug resistance. Compared to parental A375 cells, A375-DacR cells exhibited a notable G₀/G₁ phase arrest. Following targeted inhibition of ABCB1, the expression of its encoded protein P-gp was reduced, leading to a decreased survival rate and clonogenic capacity of A375-DacR cells upon dacarbazine treatment. Conclusion Following long-term induction, the A375-DacR cell population exhibited a transition into the quiescent phase (G₀ phase) as an adaptive response to the selective pressure of dacarbazine treatment. Moreover, the high expression of the ABCB1 gene and its encoded protein P-gp was identified as a key driver of dacarbazine resistance in melanoma A375-resistant cells. Inhibition of ABCB1 effectively restored the sensitivity of A375-DacR cells to dacarbazine. This study suggests that targeting ABCB1 may serve as an effective strategy for overcoming dacarbazine resistance in melanoma therapy.

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melanoma A375 cells / dacarbazine / drug-resistant cell line / abcb1 / drug resistance / targeted reversal

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LIAO Yilong, DENG Yuanxiong. Analysis of dacarbazine resistance in melanoma mediated by abcb1 overexpression and its reversal through targeted inhibition[J]. Journal of Hunan Normal University(Medical Science). 2025, 22(3): 8-14

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