乳酸脱氢酶
乳酸脱氢酶A
糖酵解
化学
肿瘤微环境
免疫系统
癌细胞
厌氧糖酵解
重编程
生物化学
癌症
细胞生物学
癌症研究
酶
新陈代谢
细胞
生物
免疫学
遗传学
作者
Suxing Jin,Enmao Yin,Changyun Feng,Yeqing Sun,Tao Yang,Hao Yuan,Zhen Guo,Xiaoyong Wang
出处
期刊:Chemical Science
[The Royal Society of Chemistry]
日期:2023-01-01
卷期号:14 (31): 8327-8337
被引量:5
摘要
Lactate dehydrogenase (LDH) is a key enzyme involved in the process of glycolysis, assisting cancer cells to take in glucose and generate lactate, as well as to suppress and evade the immune system by altering the tumor microenvironment (TME). Platinum(iv) complexes MDP and DDP were prepared by modifying cisplatin with diclofenac at the axial position(s). These complexes exhibited potent antiproliferative activity against a panel of human cancer cell lines. In particular, DDP downregulated the expression of LDHA, LDHB, and MCTs to inhibit the production and influx/efflux of lactate in cancer cells, impeding both glycolysis and glucose oxidation. MDP and DDP also reduced the expression of HIF-1α, ARG1 and VEGF, thereby disrupting the formation of tumor vasculature. Furthermore, they promoted the repolarization of macrophages from the tumor-supportive M2 phenotype to the tumor-suppressive M1 phenotype in the TME, thus enhancing the antitumor immune response. The antitumor mechanism involves reprogramming the energy metabolism of tumor cells and relieving the immunosuppressive TME.
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