铂基化合物通常用作结直肠癌 (CRC) 的初始治疗。然而，CRC患者耐药性的发展使得在临床治疗期间需要施用高浓度的药物，从而增加了铂类化合物的毒性并增加了死亡率。 STAG2是许多癌症中显着相关的耐药基因，但尚未在结直肠癌中进行研究。因此，本研究旨在探讨顺铂耐药基因STAG2的作用和药物敏感性。利用癌症药物敏感性基因组学（GDSC）和Kaplan研究STAG2对CRC患者耐药性和生存率的影响-Meier (KM) 绘图仪数据库。随后，使用STAG2的敲低测试生成sh-STAG2-HT-29细胞系，并使用细胞活力测试确定两种细胞系的半数最大抑制浓度（IC50）。然后我们使用了各种技术，包括细胞计数试剂盒-8 (CCK-8)、板克隆、5-乙炔基-2'-脱氧尿苷 (EdU) 荧光染色、用于细胞周期检测的流式细胞术、疤痕测定、Transwell 侵袭实验，以及用于细胞凋亡检测的膜联蛋白 V-异硫氰酸荧光素 (FITC)/碘化丙啶 (PI) 荧光染色，以研究四个亚组癌细胞系的功能。此外，蛋白质印迹（WB）用于识别与观察到的功能改变相关的潜在途径。最后，使用皮下成瘤方法评估所形成肿瘤的表型、肿瘤重量、小鼠重量、肿瘤体积和肿瘤组织结构。数据库分析表明，STAG2在促进CRC个体的耐药性中发挥作用。此外，该基因的突变导致对顺铂的敏感性增加，其过度表达与不良预后相关。成功开发 STAG2 敲低细胞后，观察到 HT-29 和 sh-STAG2-HT-29 细胞之间 IC50 浓度存在差异。选择10 μM顺铂治疗浓度，敲低STAG2后癌细胞的增殖、迁移和侵袭能力下降。此外，细胞对顺铂治疗的敏感性增加，这可能是由上皮间质转化（EMT）途径介导的。在小鼠中，敲低STAG2可降低HT-29细胞的致瘤潜力，同时伴随着对顺铂治疗的耐药性降低。STAG2在CRC中作为原癌基因，其对顺铂治疗的耐药性更为突出。该研究证实了STAG2在CRC中的作用，为进一步开发STAG2作为患者接受铂类药物治疗时确定剂量的辅助标准提供了理论基础。如有任何疑问，请发送电子邮件至 epub@benthamscience.net。

Platinum-based compounds are commonly used as an initial treatment for colorectal cancer (CRC). However, the development of drug resistance in patients with CRC necessitates the administration of high drug concentrations during clinical treatment, thereby augmenting the toxicity of platinum-based compounds and increasing the mortality rate. STAG2 is a significantly associated drug-resistance gene in many cancers, but it has not been studied in colorectal cancer. Therefore, the present study aimed to investigate the role and drug sensitivity of the cisplatin-resistant gene STAG2.The effects of STAG2 on drug resistance and survival rates of patients with CRC were examined using the Genomics of Drug Sensitivity in Cancer (GDSC) and Kaplan-Meier (KM) plotter databases. Subsequently, a sh-STAG2-HT-29 cell line was generated using a knockdown test of STAG2, and the half-maximal inhibitory concentration (IC50) of the two cell lines was determined using a cell viability test. We then used various techniques, including the Cell Counting Kit-8 (CCK-8), plate cloning, 5-ethynyl-2'-deoxyuridine (EdU) fluorescence staining, flow cytometry for cell cycle detection, the scar assay, the Transwell invasion assay, and Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) fluorescence staining for apoptosis detection, to investigate the functionality of the four subgroups of cancer cell lines. Additionally, Western blotting (WB) was used to identify the potential pathways associated with the observed functional alterations. Finally, the phenotype, tumor weight, mouse weight, tumor volume, and tumor tissue structure of the developed tumors were assessed using the subcutaneous tumor formation method.Database analysis indicated that STAG2 plays a role in facilitating drug resistance among individuals with CRC. Furthermore, mutations in this gene lead to increased sensitivity to cisplatin, and its overexpression was associated with an unfavorable prognosis. Following the successful development of STAG2 knockdown cells, differences in IC50 concentrations were observed between HT-29 and sh-STAG2-HT-29 cells. A treatment concentration of 10 μM cisplatin was selected, and the proliferation, migration, and invasion capabilities of cancer cells decreased after STAG2 knockdown. Additionally, the sensitivity of the cells to cisplatin therapy was increased, which was potentially mediated by the epithelial-mesenchymal transition (EMT) pathway. In mice, the tumorigenic potential of HT-29 cells was reduced by STAG2 knockdown, accompanied by a decrease in resistance to cisplatin therapy.STAG2 acts as a proto-oncogene in CRC, and its resistance to cisplatin therapy is more prominent. This study confirmed the role of STAG2 in CRC and provided a theoretical basis for the further development of STAG2 as an auxiliary criterion for determining dosage when patients are treated with platinum drugs.Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.