乳酸脱氢酶（LDH）是参与糖酵解过程的关键酶，它协助癌细胞吸收葡萄糖并产生乳酸，同时通过改变肿瘤微环境（TME）来抑制和逃避免疫系统。铂(iv)络合物MDP和DDP是通过在轴位上用双氯芬酸改性顺铂而制备的。这些络合物对一系列人类癌细胞株表现出强大的抗增殖活性。特别是DDP通过下调LDHA、LDHB和MCTs的表达来抑制癌细胞内乳酸的产生和流入/流出，从而阻碍糖酵解和葡萄糖氧化。MDP和DDP还减少了HIF-1α、ARG1和VEGF的表达，从而破坏了肿瘤血管的形成。此外，它们促进了肿瘤支持性M2型巨噬细胞向肿瘤抑制性M1型巨噬细胞的极化转化，从而增强了抗肿瘤免疫应答。抗肿瘤机制涉及重编程肿瘤细胞的能量代谢和改善免疫抑制的TME。本期刊为Royal Society of Chemistry所有。

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.This journal is © The Royal Society of Chemistry.