Endothelin-3/endothelin receptor B(ET-3/ETRB) regulates the NF-κB/Bfl-1 anti-apoptotic pathway in a malignant melanoma cell line A375
10.3760/cma.j.issn.0412-4030.2011.03.012
- VernacularTitle: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
- Author:
Lingyun YANG
;
Yanqiu LI
;
Wei HUANG
;
Shanying ZENG
;
Cuiyan WANG
;
Lan SUN
;
Li ZHU
;
Yun LIN
;
Changzheng HUANG
;
Siyuan CHEN
- Publication Type:Journal Article
- Keywords:
Melanoma,experimental;
Endothelin-3;
Receptor,endothelin B;
NF-kappa B
- From:
Chinese Journal of Dermatology
2011;44(3):191-194
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the modulation of ET-3 on the nuclear factor (NF)-κB/Bfl-1 antiapoptotic 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.
