Zhao Liangcai, Zhou Yiming, Bai Zhibin, Zhang Feng, Yang Xiaoming
Image-Guided Biomolecular Intervention Research, Section of Interventional Radiology, Department of Radiology, University of Washington School of Medicine, Seattle, WA, USA.
School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China.
J Interv Med. 2022 May 21;5(2):57-63. doi: 10.1016/j.jimed.2022.02.002. eCollection 2022 May.
To investigate the underlying molecular mechanisms of radiofrequency hyperthermia (RFH)-enhanced direct chemotherapy of pancreatic cancers.
Rat ductal PaCa cell line DSL-6A/C1 and orthotopic pancreatic cancers of Lewis rats were divided into four study groups with various treatments: i) phosphate-buffered saline (PBS) as a control; ii) RFH alone; iii) intratumoral chemotherapy alone (gemcitabine); and (iv) combination therapy of gemcitabine plus intratumoral RFH at 42 °C for 30 min. In the in-vitro confirmation experiments, the viability and apoptosis of DSL-6A/C1 cells in each treatment group were evaluated using cell live/dead staining, flow cytometry, and Western blot. In the in vivo validation experiments, related proteins were evaluated by immunohistochemistry (IHC) staining of tumors.
Of the in-vitro experiments, the lowest cell viability and more apoptotic cells were shown in the group with combination therapy compared to other treatments. Western blot data showed elevated Bax/Bcl-2, Caspase-3, and HSP70 expressions in DSL cells with combination therapy, compared to other treatments. Of the in vivo experiments, IHC staining detected the significantly increased expressions of HSP70, IL-1β, TNF-ɑ, Bax, and Caspase-3 in pancreatic cancer tissues of the animal group treated by combination therapy of gemcitabine with RFH.
Molecular imaging-guided interventional RFH can significantly enhance the chemotherapeutic effect on pancreatic cancers via potential molecular mechanisms of up-regulating Bax/caspase-3-dependent apoptosis pathways.
探讨射频热疗（RFH）增强胰腺癌直接化疗的潜在分子机制。
将大鼠导管胰腺癌细胞系DSL-6A/C1和Lewis大鼠原位胰腺癌分为四个研究组，分别进行不同处理：i）磷酸盐缓冲盐水（PBS）作为对照；ii）单纯RFH；iii）单纯瘤内化疗（吉西他滨）；iv）吉西他滨联合瘤内42℃、30分钟的RFH治疗。在体外验证实验中，使用细胞活/死染色、流式细胞术和蛋白质免疫印迹法评估各治疗组DSL-6A/C1细胞的活力和凋亡情况。在体内验证实验中，通过肿瘤的免疫组织化学（IHC）染色评估相关蛋白。
在体外实验中，与其他治疗相比，联合治疗组的细胞活力最低，凋亡细胞更多。蛋白质免疫印迹数据显示，与其他治疗相比，联合治疗的DSL细胞中Bax/Bcl-2、Caspase-3和HSP70表达升高。在体内实验中，免疫组织化学染色检测到吉西他滨与RFH联合治疗的动物组胰腺癌组织中HSP70、IL-1β、TNF-α、Bax和Caspase-3的表达显著增加。
分子成像引导的介入性RFH可通过上调Bax/caspase-3依赖性凋亡途径的潜在分子机制，显著增强对胰腺癌的化疗效果。
