Xiao Ming-Bing, Jin Dan-Dan, Jiao Yu-Jie, Ni Wen-Kai, Liu Jin-Xia, Qu Li-Shuai, Lu Cui-Hua, Ni Run-Zhou, Jiang Feng, Chen Wei-Chang
Department of Gastroenterology, The First Affiliated Hospital of Soochow University, No. 188, Shizi Road, Suzhou, 215006, Jiangsu, People's Republic of China.
Department of Gastroenterology, Affiliated Hospital of Nantong University, No. 20, Xisi Road, Nantong, 226001, Jiangsu, People's Republic of China.
Mol Biol Rep. 2018 Dec;45(6):1863-1871. doi: 10.1007/s11033-018-4332-3. Epub 2018 Oct 10.
Psychological stress has been recognized as a well-documented risk factor associated with β2-adrenergic receptor (β2-AR) in the development of pancreatic cancer. Aldo-keto reductase 1 member B1 (AKR1B1) is a potential interacting partner of β2-AR, but the effect of their interaction on pancreatic cancer cells is not known at present. We found a positive correlation between AKR1B1 and β2-AR expression in pancreatic cancer tissue samples, and co-localization of these proteins in the human pancreatic cancer BXPC-3 cell line. Compared to the controls, the CFPAC-1 and PANC-1 pancreatic cancer cells overexpressing β2-AR and AKR1B1 respectively showed significantly higher proliferation rates, which is attributed to higher proportion of cells in the S phase and decreased percentage of early apoptotic cells. Furthermore, overexpression of β2-AR led to a significant increase in the expression of AKR1B1 and phosphorylated extracellular signal-regulated kinase (p-ERK1/2). Overexpression of AKR1B1 significantly decreased β2-AR levels and increased that of p-ERK1/2. Taken together, β2-AR directly interacted with and up-regulated AKR1B1 in pancreatic cancer cells, and promoted their proliferation and inhibited apoptosis via the ERK1/2 pathway. Our findings also highlight the β2-AR-AKR1B1 axis as a potential therapeutic target for pancreatic cancer.
心理压力已被公认为是与胰腺癌发生发展中β2 - 肾上腺素能受体（β2 - AR）相关的一个有充分文献记载的风险因素。醛糖还原酶1家族成员B1（AKR1B1）是β2 - AR的一个潜在相互作用伙伴，但它们之间的相互作用对胰腺癌细胞的影响目前尚不清楚。我们发现胰腺癌组织样本中AKR1B1与β2 - AR表达呈正相关，且这些蛋白在人胰腺癌BXPC - 3细胞系中共定位。与对照组相比，分别过表达β2 - AR和AKR1B1的CFPAC - 1和PANC - 1胰腺癌细胞显示出显著更高的增殖率，这归因于S期细胞比例更高以及早期凋亡细胞百分比降低。此外，β2 - AR的过表达导致AKR1B1和磷酸化细胞外信号调节激酶（p - ERK1/2）的表达显著增加。AKR1B1的过表达显著降低β2 - AR水平并增加p - ERK1/2水平。综上所述，β2 - AR在胰腺癌细胞中直接与AKR1B1相互作用并上调其表达，并通过ERK1/2途径促进细胞增殖和抑制凋亡。我们的研究结果还突出了β2 - AR - AKR1B1轴作为胰腺癌潜在治疗靶点的作用。
