艾氏腹水癌及其皮下接种形式的实体肿瘤（SEC）是探索化疗分子靶点的可靠模型。针对内在细胞凋亡的分子靶点，如调节半胱氨酸蛋白酶激活剂第二种线粒体（SMAC），发现了新的化疗方法。SMAC是丝裂原活化蛋白激酶（MAPKs）的生理底物。谷胱甘肽S-转移酶P1（GSTP1）及其与MAPKs的密切关联在恶性细胞增殖、转移和耐药中起着重要作用。硝唑酮（NTZ）是新兴的癌症治疗方法，其针对的GSTP1证据仍然需要深入研究。 在经过小鼠接种的SEC模型中，通过测量肿瘤质量、肿瘤MAPKs、细胞色素c、Bcl-2相互作用的细胞死亡介导物（BIM）和SMAC信号通路以及其分子下游半胱氨酸蛋白酶3和9的变化，评估口服NTZ（200mg/kg/天）和5-氟尿嘧啶（5-FU；20mg/kg/天，腹腔注射）治疗方案的化疗作用。这些靶蛋白相互作用的计算分析显示直接有序的相互作用。在单独使用NTZ和5-FU治疗方案后，提取的肿瘤碟的组织形态学结构显示存活肿瘤区域减少，并带有明显的坏死周围。这些发现与肿瘤大小一致。每个独立的方案降低了EST组织中明显的GSTP1并提高了低的MAPKs表达、细胞色素c、BIM、SMAC和半胱氨酸蛋白酶3和9的表达。 NTZ在SEC中的化疗活性得到了证实。此外，NTZ具有SMAC调节活性，应在深入研究后作为治疗实体瘤的一种化疗方法。版权所有 © 2023 Elsevier Inc.

Ehrlich ascites carcinoma and its subcutaneous inoculated solid tumour form (SEC) are reliable models for chemotherapeutic molecular targets exploration. Novel chemotherapeutic approaches are identified as molecular targets for intrinsic apoptosis, like the modulation of the second mitochondria-derived activator of caspases (SMAC). SMAC is a physiological substrate of mitogen-activated protein kinases (MAPKs). Glutathione-S-transferase P1 (GSTP1) and its close association with MAPKs play an important role in malignant cell proliferation, metastasis, and resistance to chemotherapeutics. Nitazoxanide (NTZ) is an emerging cancer therapy and its targeted GSTP1 evidence remains a knowledge need.In the present mice-established SEC, the chemotherapeutic roles of oral NTZ (200 mg/kg/day) and 5-fluorouracil (5-FU; 20 mg/kg/day, intraperitoneally) regimens were evaluated by measuring changes in tumour mass, the tumour MAPKs, cytochrome c, Bcl-2 interacting mediator of cell death (BIM), and SMAC signalling pathway in addition to its molecular downstream; caspases 3 and 9.Computational analysis for these target protein interactions showed direct-ordered interactions. After individual therapy with NTZ and 5-FU regimens, the histological architecture of the extracted tumour discs revealed decreases in viable tumour regions with significant necrosis surrounds. These findings were consistent with gross tumour sizes. Each separate regimen lowered the remarkable GSTP1 and elevated the low MAPKs expressions, cytochrome c, BIM, SMAC, and caspases 3, and 9 in EST tissues.The chemotherapeutic activity of NTZ in SEC was proven. Additionally, NTZ possesses a SMAC modulatory activity that, following thorough research, should be taken into consideration as a chemotherapeutic approach in solid tumours.Copyright © 2023 Elsevier Inc. All rights reserved.