Ning Zhouyu, Zhu Zhenfeng, Wang Haiyong, Zhang Chenyue, Xu Litao, Zhuang Liping, Yan Xia, Wang Dan, Wang Peng, Meng Zhiqiang
Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China,
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China,
Onco Targets Ther. 2019 Feb 12;12:1161-1170. doi: 10.2147/OTT.S185953. eCollection 2019.
High-intensity focused ultrasound (HIFU) has the potential to be an effective therapeutic strategy for pancreatic cancer (PC). However, owing to the high malignancy and poor prognosis of PC, the use of HIFU therapy alone is not sufficient to impair the progression of PC. Bufalin, a compound extracted from traditional medicine, is known to inhibit the growth and progression of PC cells. However, the effect of the combination therapy of HIFU plus bufalin (HIFU+bufalin) is still uncertain.
A colony formation assay and flow cytometry were performed to measure the growth and induction of apoptosis in PC cells. Western blotting was used to explore the potential mechanism of HIFU and bufalin therapy. The in vivo efficacy of HIFU+bufalin was tested in a MiaPaCa xenograft model.
Bufalin inhibited the growth of PC cells more obviously compared to HIFU. Combining bufalin with HIFU further decreased the growth of MiaPaCa cells compared with single therapy in vitro. Flow cytometry results showed that the percentage of surviving MiaPaCa cells in the bufalin-treated group and the HIFU-treated group was approximately three-fold and two-fold higher than in the HIFU+bufalin-treated group. Contrasting results were found in Panc-1 cells. Biochemical analysis revealed that HIFU+bufalin treatment elevated PARP expression and increased caspase-8 activation in MiaPaCa and Panc-1 cells. HIFU+bufalin significantly reduced the growth of MiaPaCa tumors compared with HIFU or bufalin treatment alone. HIFU+bufalin treatment decreased Ki67 staining and increased activated caspase-3 and caspase 8 staining, when compared with HIFU or bufalin treatment alone in mouse tumors.
HIFU enhanced the effect of bufailn by inducing apoptosis in PC cells. A combination of HIFU and bufalin may be employed as an alternative therapeutic strategy for PC.
高强度聚焦超声（HIFU）有可能成为一种有效的胰腺癌（PC）治疗策略。然而，由于PC的高恶性和预后不良，单独使用HIFU治疗不足以抑制PC的进展。蟾毒灵是一种从传统药物中提取的化合物，已知可抑制PC细胞的生长和进展。然而，HIFU联合蟾毒灵（HIFU + 蟾毒灵）的联合治疗效果仍不确定。
进行集落形成试验和流式细胞术以测量PC细胞的生长和凋亡诱导。蛋白质印迹法用于探索HIFU和蟾毒灵治疗的潜在机制。在MiaPaCa异种移植模型中测试了HIFU + 蟾毒灵的体内疗效。
与HIFU相比，蟾毒灵更明显地抑制了PC细胞的生长。与体外单一治疗相比，将蟾毒灵与HIFU联合使用进一步降低了MiaPaCa细胞的生长。流式细胞术结果显示，蟾毒灵治疗组和HIFU治疗组中存活的MiaPaCa细胞百分比比HIFU + 蟾毒灵治疗组高约三倍和两倍。在Panc - 1细胞中发现了相反的结果。生化分析表明，HIFU + 蟾毒灵治疗提高了PARP表达，并增加了MiaPaCa和Panc - 1细胞中caspase - 8的激活。与单独的HIFU或蟾毒灵治疗相比，HIFU + 蟾毒灵显著降低了MiaPaCa肿瘤的生长。与单独的HIFU或蟾毒灵治疗相比，HIFU + 蟾毒灵治疗降低了小鼠肿瘤中的Ki67染色，并增加了活化的caspase - 3和caspase 8染色。
HIFU通过诱导PC细胞凋亡增强了蟾毒灵的作用效果。HIFU和蟾毒灵的联合使用可能作为PC的替代治疗策略。
