放射抵抗是影响结直肠癌（CRC）治疗结果的关键因素。黄芩素 (BE) 主要源自黄芩，已显示出抗 CRC 特性。然而，BE 对 CRC 放射敏感性的影响仍不清楚。本研究旨在评估BE在CRC放疗中的放射增敏作用并阐明其机制。我们使用受到电离辐射 (IR) 的亲本 CRC 细胞 (CT26) 建立了体外抗辐射细胞模型 (CT26-R)。 CT26-R细胞用或不用BE预处理，然后用pcDNA-NC和pcDNA-JAK2转染。使用集落形成测定评估用BE和IR处理的CT26-R细胞的增殖。通过 CT26-R 细胞移植在 BALB/c 小鼠中建立了 CRC 动物模型。 BE 对 CRC 的放射增敏作用在体内进行了评估。采用TUNEL法检测肿瘤组织的细胞凋亡情况。通过蛋白质印迹法测量体外和体内 p-STAT3、JAK2、PD-L1 和 SOCS3 的表达水平。我们的结果表明，BE 显着增加体外和体内的放射敏感性，并增强肿瘤组织的细胞凋亡。此外，BE 显着下调 p-STAT3、JAK2 和 PD-L1 的表达，并显着上调 SOCS3 的表达。 pcDNA-JAK2 可逆转这些体内效应。总之，我们的数据表明 BE 通过抑制 JAK2/STAT3 通路来增强 CRC 放射敏感性。© 2024 作者。化学生物学

Radiation resistance is a crucial factor influencing therapeutic outcomes in colorectal cancer (CRC). Baicalein (BE), primarily derived from Scutellaria baicalensis, has demonstrated anti-CRC properties. However, the impact of BE on the radiosensitivity of CRC remains unclear. This study aimed to evaluate the radiosensitization effects of BE and elucidate its mechanism in CRC radiotherapy. We established an in vitro radioresistant cell model (CT26-R) using parental CRC cells (CT26) subjected to ionizing radiation (IR). CT26-R cells were pretreated with or without BE, followed by transfection with pcDNA-NC and pcDNA-JAK2. The proliferation of CT26-R cells treated with BE and IR was assessed using a colony formation assay. A CRC animal model was developed in BALB/c mice via CT26-R cell transplantation. The radiosensitizing effect of BE on CRC was evaluated in vivo. TUNEL assay was conducted to detect apoptosis in tumor tissue. The expression levels of p-STAT3, JAK2, PD-L1, and SOCS3 in vitro and in vivo were measured by western blotting. Our results demonstrated that BE significantly increased radiosensitivity in vitro and in vivo and enhanced apoptosis in tumor tissues. Additionally, BE significantly downregulated the expression of p-STAT3, JAK2, and PD-L1, and significantly upregulated SOCS3 expression. These in vivo effects were reversed by pcDNA-JAK2. In summary, our data suggest that BE enhances CRC radiosensitivity by inhibiting the JAK2/STAT3 pathway.© 2024 The Author(s). Chemical Biology & Drug Design published by John Wiley & Sons Ltd.