Chetty Carryn J, Ferreira Eloise, Jovanovic Katarina, Weiss Stefan F T
School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Wits 2050, Johannesburg, Republic of South Africa.
School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Wits 2050, Johannesburg, Republic of South Africa.
Exp Cell Res. 2017 Nov 15;360(2):264-272. doi: 10.1016/j.yexcr.2017.09.016. Epub 2017 Sep 10.
The 37kDa/67kDa laminin receptor (LRP/LR) serves various physiological and pathological roles such as enhancing tumour-related processes including metastasis, angiogenesis, cellular viability and telomerase activation in cancerous cell lines. The present study investigates the effect of siRNA mediated downregulation of LRP/LR on pancreatic cancer (AsPC-1) and neuroblastoma (IMR-32) cells. MTT and BrdU assays revealed that siRNA mediated downregulation of LRP resulted in a significant reduction in cell viability and cell proliferation. In addition, knock-down of LRP resulted in phosphatidylserine externalization, diminished nuclear integrity and significantly enhanced caspase-3 activity, which is indicative of apoptosis. LRP downregulation resulted in a significant increase in caspase-8 activity in IMR-32 cells and enhanced caspase-8 and 9 activity in AsPC-1 cells. These data recommend siRNA mediated knock-down of LRP as a potential therapeutic avenue for the treatment of pancreatic cancer and neuroblastoma.
37kDa/67kDa层粘连蛋白受体（LRP/LR）发挥着多种生理和病理作用，比如在癌细胞系中增强包括转移、血管生成、细胞活力和端粒酶激活等与肿瘤相关的过程。本研究调查了小干扰RNA（siRNA）介导的LRP/LR下调对胰腺癌细胞（AsPC-1）和成神经细胞瘤细胞（IMR-32）的影响。MTT和BrdU检测显示，siRNA介导的LRP下调导致细胞活力和细胞增殖显著降低。此外，LRP的敲低导致磷脂酰丝氨酸外化、核完整性受损，并显著增强了半胱天冬酶-3活性，这表明细胞发生了凋亡。LRP下调导致IMR-32细胞中半胱天冬酶-8活性显著增加，并增强了AsPC-1细胞中半胱天冬酶-8和-9的活性。这些数据表明，siRNA介导的LRP敲低是治疗胰腺癌和成神经细胞瘤的一种潜在治疗途径。
