Role of MSX2 in melanoma cells for trametinib resistance

doi:10.12092/j.issn.1009-2501.2019.10.010

Abstract

Abstract:

AIM: To study the role of homeobox gene MSX2 in the melanoma cell line A375 of trametinib resistance. METHODS: To construct trametinib resistant A375 cell line (A375-AR). After trametinib intervented A375 and A375-AR，the cell viability was detected by CCK-8, the cell apoptosis rate was detected by flow cytometry, and the expression of Bcl-2, Bax, Caspase-3, Caspase-9 and MSX2 in the cells were detected by Western blot. Small interfering RNA (siRNA) was used to silence MSX2 gene in A375-AR. After trametinib intervented A375 and A375-AR，the cell viability was detected by CCK-8, the cell apoptosis rate was detected by flow cytometry, and the expression of Bcl-2, Bax, Caspase-3, Caspase-9 and MSX2 in the cells were detected by Western blot. To construct MSX2 over-expressing A375 cell line (A375-OE), and A375, A375-OE and A375-AR groups were set up. After trametinib intervented A375 and A375-AR，the cell viability was detected by CCK-8, the cell apoptosis rate detected by flow cytometry, and the expression of Bcl-2, Bax, Caspase-3, Caspase-9 and MSX2 in the cells were detected by Western blot. RESULTS:A375-AR was resistant to trametinib of 1.8 nmol/L, the activity of A375 cells and the rate of cell apoptosis were significantly higher than that of A375-AR, and the expression level of Bcl-2 gene in A375 cells was lower than that of A375-AR, while the expression level of Bax, Caspase-3 and Caspase-9 was higher than that of A375-AR. After A375-AR silenced of MSX2, the cells were significantly increased to the sensibility of trametinib, the apoptosis rate was up-regulated, the expression of Bcl-2 in the cells was down-regulated, and the expression of Bax, Caspase-3 and Caspase-9 was up-regulated. After A375 overexpression of MSX2, the cells were down regulated to the sensibility of trametinib, the cell viability was up-regulated, the apoptosis rate was down-regulated, the expression of Bcl-2 in the cells was up-regulated, and the expression of Bax, Caspase-3 and Caspase-9 was down regulated. CONCLUSION: MSX2 gene can induce the resistance of melanoma cells to trametinib. It is a potential target for the treatment of melanoma resistance.

Key words: homeobox gene MSX2, melanoma, trametinib, drug resistance

CLC Number:

R966
R739.5

WANG Xiaoli, LU Shuping, DAI Jiale. Role of MSX2 in melanoma cells for trametinib resistance[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(10): 1147-1154.

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