School of Biotechnology, Banaras Hindu University, Varanasi, 221 005, UP, India.
Mol Carcinog. 2013 Dec;52(12):932-45. doi: 10.1002/mc.21922. Epub 2012 May 7.
Using a murine tumor model, we demonstrate that tumor cells display a tumor stage-dependent differential glucose utilization associated with an altered GLUT-1 expression. Hyperglycemic tumor microenvironment modulates the tumorigenic ability, survival, apoptosis, and glucose utilization of tumor cells in late tumor-bearing stage accompanied by an altered tumor acidosis and expression of cell survival regulatory molecules: HIF-1α, p53, Bcl2, caspase-activated DNase, IL-4, IL-6, IL-10, IFN-γ, TGF-β, and VEGF. Glucose-exposed tumor cells of late tumor-bearing stage also show a declined susceptibility to the cytotoxic action of chemotherapeutic drugs: cisplatin and methotrexate, accompanied by an increased expression of MDR-1 gene. Taken together the results show that hyperglycemic tumor microenvironment differentially alters tumor growth depending on the stage of tumor progression.
利用小鼠肿瘤模型，我们证明肿瘤细胞表现出与 GLUT-1 表达改变相关的肿瘤阶段依赖性葡萄糖利用差异。高血糖肿瘤微环境调节晚期荷瘤阶段肿瘤细胞的致瘤能力、存活、凋亡和葡萄糖利用，伴随肿瘤酸中毒和细胞存活调节分子表达的改变：HIF-1α、p53、Bcl2、caspase 激活的脱氧核糖核酸酶、IL-4、IL-6、IL-10、IFN-γ、TGF-β和 VEGF。晚期荷瘤阶段暴露于葡萄糖的肿瘤细胞对顺铂和甲氨蝶呤等化疗药物的细胞毒性作用的敏感性也降低，同时 MDR-1 基因的表达增加。总之，这些结果表明高血糖肿瘤微环境根据肿瘤进展的阶段差异改变肿瘤生长。
