■越来越多的证据表明癌症代谢重编程与氧化还原稳态的改变有关。戊糖磷酸途径(PPP)是促进癌症生长的关键代谢相关途径之一。该途径的葡萄糖6-磷酸脱氢酶(G6PD)产生还原的烟酰胺腺嘌呤二核苷酸磷酸(NADPH),这对于控制细胞氧化还原稳态至关重要。
■本研究旨在探讨G6PD对非小细胞肺癌(NSCLC)的生长促进作用。
■在朱拉隆功国王纪念医院诊断为肺癌的64例患者的临床特征和肺组织中G6PD表达水平(曼谷,泰国)在2009-2014年期间进行了分析。NSCLC细胞系中的G6PD活性,包括NCI-H1975和NCI-H292,使用DHEA和siG6PD进行实验抑制,以研究癌细胞增殖和迁移。
■用免疫组织化学染色检测到G6PD在NSCLC组织中的阳性表达,发现与鳞状细胞有关。G6PD表达水平和活性也与NSCLC细胞系的增殖率一致。通过增加Bax/Bcl-2比例表达抑制G6PD诱导的NSCLC细胞凋亡。添加D-(-)-核糖,这是PPP的最终产品,增加G6PD缺陷型NSCLC细胞系的存活率。
■集体,这些发现表明G6PD可能在NSCLC的癌变过程中起重要作用。抑制G6PD可能为NSCLC的治疗提供治疗策略。
UNASSIGNED: Mounting evidence has linked cancer metabolic reprogramming with altered redox homeostasis. The pentose phosphate pathway (PPP) is one of the key metabolism-related pathways that has been enhanced to promote cancer growth. The glucose 6-phosphate dehydrogenase (G6PD) of this pathway generates reduced nicotinamide adenine dinucleotide phosphate (NADPH), which is essential for controlling cellular redox homeostasis.
UNASSIGNED: This research aimed to investigate the growth-promoting effects of G6PD in non-small cell lung cancer (NSCLC).
UNASSIGNED: Clinical characteristics and G6PD expression levels in lung tissues of 64 patients diagnosed with lung cancer at the King Chulalongkorn Memorial Hospital (Bangkok, Thailand) during 2009-2014 were analyzed. G6PD activity in NSCLC cell lines, including NCI-H1975 and NCI-H292, was experimentally inhibited using DHEA and siG6PD to study cancer cell proliferation and migration.
UNASSIGNED: The positive expression of G6PD in NSCLC tissues was detected by immunohistochemical staining and was found to be associated with squamous cells. G6PD expression levels and activity also coincided with the proliferation rate of NSCLC cell lines. Suppression of G6PD-induced apoptosis in NSCLC cell lines by increasing Bax/Bcl-2 ratio expression. The addition of D-(-)-ribose, which is an end-product of the PPP, increased the survival of G6PD-deficient NSCLC cell lines.
UNASSIGNED: Collectively, these findings demonstrated that G6PD might play an important role in the carcinogenesis of NSCLC. Inhibition of G6PD might provide a therapeutic strategy for the treatment of NSCLC.