Background/Objectives: Identifying novel targets to treat gastric cancer (GC) has become a focus of research in recent years. Our acceleratedHelicobacter-induced gastric cancer mouse model allowed us to identify several differentially expressed genes (DEGs), includingPsmb8(proteasome subunit beta type 8, also called Lmp7), which was also found to be elevated in GC patient samples.PSMB8encodes one of the immune subunits of the immunoproteasome, which has been associated with disease severity in multiple cancers.Methods:We identified carfilzomib from a public database as a potential drug targetingPSMB8; it effectively halts immunoproteasome activity, leading to apoptosis. We tested carfilzomib’s efficacy against gastric cancer by subcutaneously implanting nude mice with human gastric epithelial-derived tumors and treating them with carfilzomib, either alone or in combination with 5-fluorouracil (5-FU), a standard-of-care drug. The effectiveness of drug treatment was measured by tumor growth, cell proliferation, and apoptosis.Results:We observed that carfilzomib retarded tumor growth, inhibited cell proliferation, and induced apoptosis.Conclusions:These results strongly suggest thatPSMB8is a suitable candidate for targeted therapy. Moreover, with carfilzomib having robust anti-tumor activity, it has potential as a treatment option for cancers where high levels ofPSMB8are associated with poor overall survival.
背景/目的：近年来，寻找治疗胃癌（GC）的新靶点已成为研究热点。通过加速幽门螺杆菌诱导的胃癌小鼠模型，我们鉴定出多个差异表达基因（DEGs），其中包括Psmb8（蛋白酶体β亚基8型，亦称Lmp7），该基因在胃癌患者样本中也呈现高表达。PSMB8编码免疫蛋白酶体的一个免疫亚基，该亚基与多种癌症的疾病严重程度相关。 方法：我们通过公共数据库确定卡非佐米为靶向PSMB8的潜在药物；该药物能有效抑制免疫蛋白酶体活性，从而诱导细胞凋亡。我们通过将人胃上皮来源肿瘤皮下植入裸鼠体内，并单独使用卡非佐米或联合标准治疗药物5-氟尿嘧啶（5-FU）进行治疗，以评估卡非佐米对胃癌的疗效。通过肿瘤生长、细胞增殖和凋亡情况来评估药物治疗效果。 结果：我们观察到卡非佐米能延缓肿瘤生长、抑制细胞增殖并诱导细胞凋亡。 结论：这些结果有力表明PSMB8是靶向治疗的合适候选靶点。此外，鉴于卡非佐米具有显著的抗肿瘤活性，对于PSMB8高表达与患者总体生存率低下相关的癌症类型，该药物具有潜在的治疗价值。
Repurposing Carfilzomib as a Promising Drug for Targeted Therapy in Gastric Cancer
肿瘤(癌症)患者之家