Duong Hong-Quan, You Kyu Sic, Oh Seunghoon, Kwak Sahng-June, Seong Yeon-Sun
Department of Cancer Research, Vinmec Research Institute of Stem Cell and Gene Technology, 458 Minh Khai, Hanoi 10000, Vietnam.
Institute of Research and Development, Duy Tan University, K7/25 Quang Trung, Danang 59000, Vietnam.
Antioxidants (Basel). 2017 Jul 1;6(3):52. doi: 10.3390/antiox6030052.
Pancreatic cancer remains an intractable cancer with a poor five-year survival rate, which requires new therapeutic modalities based on the biology of pancreatic oncogenesis. Nuclear factor E2 related factor-2 (NRF2), a key cytoprotective nuclear transcription factor, regulates antioxidant production, reduction, detoxification and drug efflux proteins. It also plays an essential role in cell homeostasis, cell proliferation and resistance to chemotherapy. We aimed to evaluate the possibility that modulation of NRF2 expression could be effective in the treatment of pancreatic cancer cells. We investigated whether the depletion of NRF2 by using small interfering RNAs (siRNAs) is effective in the expression of biomarkers of pancreatic cancer stemness such as aldehyde dehydrogenase 1 family, member A1 (ALDH1A1) and aldehyde dehydrogenase 3 family, member A1 (ALDH3A1). NRF2 knockdown markedly reduced the expression of NRF2 and glutamate-cysteine ligase catalytic subunit (GCLC) in cell lines established from pancreatic cancers. NRF2 silencing also decreased the ALDH1A1 and ALDH3A1 expression. Furthermore, this NRF2 depletion enhanced the antiproliferative effects of the chemotherapeutic agent, 5-fluorouracil (5-FU) in pancreatic cancer cells.
胰腺癌仍然是一种难以治疗的癌症，五年生存率很低，这需要基于胰腺肿瘤发生生物学的新治疗方法。核因子E2相关因子2（NRF2）是一种关键的细胞保护核转录因子，可调节抗氧化剂的产生、还原、解毒和药物外排蛋白。它在细胞稳态、细胞增殖和化疗耐药性中也起着重要作用。我们旨在评估调节NRF2表达对治疗胰腺癌细胞是否有效。我们研究了使用小干扰RNA（siRNA）耗尽NRF2对胰腺癌干性生物标志物如醛脱氢酶1家族成员A1（ALDH1A1）和醛脱氢酶3家族成员A1（ALDH3A1）表达的影响。NRF2基因敲低显著降低了胰腺癌建立的细胞系中NRF2和谷氨酸-半胱氨酸连接酶催化亚基（GCLC）的表达。NRF2沉默也降低了ALDH1A1和ALDH3A1的表达。此外，这种NRF2耗尽增强了化疗药物5-氟尿嘧啶（5-FU）对胰腺癌细胞的抗增殖作用。
