MS-275 has been demonstrated to inhibit the growth of esophageal squamous cell carcinoma (ESCC) cells in our previous study, but its role in ESCC remains fully explored. Cisplatin (cis-diamminedichloroplatinum II, DDP) is the first line of chemotherapeutic drug widely used in clinic for ESCC patients. However, the side effects of nephrotoxicity and drug resistance limit its clinical use. This study aimed to evaluate the anticancer effects of MS-275 combined with DDP on ESCC cell line EC9706 both in vitro and in vivo, and to investigate the possible mechanisms that mediate these effects. We found that MS-275 combined with DDP showed synergistic antitumor effects on EC9706 cells in vitro by decreasing cell proliferation, increasing apoptosis and oxidative damage, and inhibiting migration and stemness. The combination of MS-275 and DDP triggered pro-survival autophagy in EC9706. Moreover, MS-275 combined with DDP suppressed EC9706 xenografts growth and promoted apoptosis in vivo. Further study displayed that MS-275 combined with DDP suppressed Wnt/β-catenin signaling in EC9706 cells and xenografts. These results indicate that MS-275 combined with DDP exerts synergistic antitumor effects by enhancing the chemosensitivity of EC9706 cells to DDP, which may be a potential therapeutic strategy for the treatment of patients with ESCC.

在我们先前的研究中，已证明MS-275可以抑制食管鳞状细胞癌（ESCC）细胞的生长，但仍在充分探索其在ESCC中的作用。顺铂（cis-diamminedichloroplatinum II，DDP）是临床上广泛用于ESCC患者的一线化疗药物。但是，肾毒性和耐药性的副作用限制了其临床应用。这项研究旨在评估MS-275与DDP联合在体外和体内对ESCC细胞EC9706的抗癌作用，并研究介导这些作用的可能机制。我们发现，MS-275与顺铂联合显示出对EC9706细胞的协同抗肿瘤作用的体外通过减少细胞增殖，增加细胞凋亡和氧化损伤，并抑制迁移和茎干。MS-275和DDP的组合在EC9706中触发了生存前自噬。此外，MS-275与DDP联合抑制EC9706异种移植物的生长并促进体内细胞凋亡。进一步的研究表明，MS-275与DDP联合可抑制EC9706细胞和异种移植物中的Wnt /β-catenin信号传导。这些结果表明，MS-275联合DDP通过增强EC9706细胞对DDP的化学敏感性发挥协同抗肿瘤作用，这可能是治疗ESCC患者的潜在治疗策略。