内皮素3/内皮素受体B对A375细胞NF-κB/ Bcl-2相关蛋白A1抗凋亡通路的调节

Abstract

Abstract:

Objective To investigate the modulation of ET-3 on the nuclear factor （NF）-κB/Bfl-1 anti-apoptotic pathway in a malignant melanoma cell line A375. Methods Flow cytometry was performed to detect the apoptosis in cultured A375 cells after treatment with ET-3 of 100 nmol/L for 24 hours. ET-3 of various concentrations （0, 1, 10, 100 nmol/L） was used to treat some A375 cells with or without the pretreatment with the ETRB antagonist BQ788; after another 24-hour culture, RT-PCR and Western blot were conducted to examine the mRNA expression of Bfl-1 and protein expressions of Bfl-1 and ETRB, respectively. Results The 24-hour treatment with ET-3 of 100 nmol/L significantly reduced the apoptosis rate of A375 cells （F = 10.68, P < 0.05）. The mRNA and protein expressions of Bfl-1 were up-regulated by ET-3 in a concentration dependent manner （both P < 0.01）, while BQ788 significantly blocked the ET-3-induced up-regulation（F = 420.38, 229.49, both P < 0.01）. The protein expression of pNF-κB in A375 cells was also enhanced by ET-3 of different concentrations （all P < 0.05）, but the enhancement was suppressed by BQ788, and there was a significant difference in the protein expression of pNF-κB between cells treated with ET-3 of 100 nmol/L and those treated with the combination of ET-3 of 100 nmol/L and BQ788 （F = 255.46, P < 0.01）. Conclusion ET-3/ETRB inhibits the apoptosis in A375 cells likely by activating the NF-κB/Bfl-1 anti-apoptotic pathway.

Key words: NF-kappa B

References

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Endothelin-3/endothelin receptor B（ET-3/ETRB） regulates the NF-κB/Bfl-1 anti-apoptotic pathway in a malignant melanoma cell line A375

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