Zhou Guanhui, Sun Bo, Zhang Feng, Ji Hongxiu, Kan Xuefeng, Yang Xiaoming
Image-Guided Bio-Molecular Intervention Research and Section of Vascular and Interventional Radiology, Department of Radiology, University of Washington School of Medicine, Seattle, WA, USA.
Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Int J Hyperthermia. 2025 Dec;42(1):2511031. doi: 10.1080/02656736.2025.2511031. Epub 2025 Jun 8.
This study evaluated whether radiofrequency hyperthermia (RFH) could enhance the effects of LTX-315, an oncolytic peptide, for hepatic cancer.
experiments using rat hepatocellular carcinoma (HCC) cells and experiments with HCC rat models were conducted. Treatments included (1) phosphate buffered saline, (2) RFH at 42 °C for 30 min, (3) LTX-315 alone, and (4) a combination of RFH with LTX-315. Cell viability and apoptosis were measured using MTS assay, flow cytometry, and fluorescence microscopy. Tumor growth was monitored for two weeks using ultrasound and optical imaging. The western blotting, enzyme-linked immunoassay, real-time polymerase chain reaction, were performed to detect the activation of cGAS-STING pathway. The immunohistochemistry, enzyme-linked immunoassay, real-time polymerase chain reaction, and flow cytometry analysis were performed to evaluate changes of immune cells in tumors, and changes of cytokines in plasma and tumors after the treatment.
The combination treatment (RFH + LTX-315) resulted in the highest level of apoptosis and the lowest cell viability, along with the smallest tumor volume and strongest reduction in bioluminescence signal compared to other groups ( < 0.001). LTX-315 activated the cGAS-STING pathway, with RFH further enhancing this activation. After combination therapy, significant increases in CD8+ T cells, CD8+/IFN-+ T cells, CD8+/TNF-+ T cells, and natural killer cells, along with a decrease in Tregs, were observed in tumors ( < 0.001).
RFH significantly enhanced the effects of LTX-315 on orthotopic HCC by activating the cGAS-STING pathway.
本研究评估射频热疗（RFH）是否能增强溶瘤肽LTX-315对肝癌的治疗效果。
进行了使用大鼠肝细胞癌（HCC）细胞的实验以及HCC大鼠模型实验。治疗方法包括（1）磷酸盐缓冲盐水，（2）42°C的RFH处理30分钟，（3）单独使用LTX-315，以及（4）RFH与LTX-315联合使用。使用MTS法、流式细胞术和荧光显微镜检测细胞活力和凋亡情况。使用超声和光学成像监测肿瘤生长两周。进行蛋白质印迹法、酶联免疫吸附测定、实时聚合酶链反应以检测cGAS-STING通路的激活情况。进行免疫组织化学、酶联免疫吸附测定、实时聚合酶链反应和流式细胞术分析以评估治疗后肿瘤中免疫细胞的变化以及血浆和肿瘤中细胞因子的变化。
与其他组相比，联合治疗（RFH + LTX-315）导致最高水平的凋亡和最低的细胞活力，同时肿瘤体积最小且生物发光信号降低最显著（<0.001）。LTX-315激活了cGAS-STING通路，RFH进一步增强了这种激活。联合治疗后，肿瘤中观察到CD8 + T细胞、CD8 + /IFN- + T细胞、CD8 + /TNF- + T细胞和自然杀伤细胞显著增加，同时调节性T细胞减少（<0.001）。
RFH通过激活cGAS-STING通路显著增强了LTX-315对原位肝癌的治疗效果。
