Abstract:
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.
摘要:
辐射抵抗是影响结直肠癌(CRC)治疗结果的关键因素。黄芩素(BE),主要来自黄芩,已经证明了抗CRC特性。然而,BE对CRC放射敏感性的影响尚不清楚.本研究旨在评估BE的放射增敏作用,并阐明其在CRC放疗中的作用机制。我们使用经受电离辐射(IR)的亲本CRC细胞(CT26)建立了体外耐放射细胞模型(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CRC动物模型。在体内评估BE对CRC的放射增敏作用。采用TUNEL法检测肿瘤组织中的细胞凋亡。通过蛋白质印迹法测量体内和体外p-STAT3、JAK2、PD-L1和SOCS3的表达水平。我们的结果表明,BE在体外和体内显着增加了放射敏感性,并增强了肿瘤组织的凋亡。此外,BE显著下调p-STAT3、JAK2和PD-L1的表达,并显著上调SOCS3的表达。这些体内作用被pcDNA-JAK2逆转。总之,我们的数据提示BE通过抑制JAK2/STAT3通路增强CRC放射敏感性.