Extracorporeal shock waves effectively suppress colorectal cancer proliferation and growth

Shock waves are widely used to treat various diseases and have numerous medical applications. In particular, extracorporeal shock waves (ESV) can substantially inhibit tumour growth. However, the therapeutic efficacy of ESV in colorectal cancer and its underlying mechanisms are not well understood. To address this gap in our knowledge, colorectal cancer cell lines HT29 and SW620 were used to generate xenograft mouse models and examined the therapeutic effects of a stepwise increase in ESV energy on tumour growth. In vivo, 60 mJ ESV significantly delayed xenograft growth compared with 120 and 240 mJ ESV, with no impact on body weight or hepatic and renal function. Transcriptome analysis revealed that 60 mJ ESV suppressed colorectal cancer cell proliferation and induced apoptosis and ferroptosis; these findings were further confirmed by immunohistochemical staining and western blotting. The in vitro study showed that ESV mechanistically suppressed cell proliferation and induced apoptosis and ferroptosis by activating the p53 signaling pathway. In conclusion, 60 mJ ESV substantially inhibited colorectal cancer growth by activating p53 pathway-related proliferation inhibition and cell death. These findings indicate that ESV therapy is a promising therapeutic strategy for colorectal cancer. RNA-Seq profiling of colorectal cancer cell line HT-29-derived xenografts from the control and 60 mJ extracorporeal shock waves (ESV) groups at day15 of 60 mJ ESV therapy.

冲击波广泛应用于多种疾病的治疗，具备诸多医学应用价值。其中，体外冲击波（extracorporeal shock waves, ESV）可显著抑制肿瘤生长。然而，体外冲击波在结直肠癌中的治疗效果及其潜在作用机制仍未被充分阐释。为填补这一研究空白，本研究采用结直肠癌细胞系HT29与SW620构建异种移植小鼠模型，探究逐步提升ESV能量对肿瘤生长的治疗效应。体内实验结果表明，与120 mJ、240 mJ ESV处理组相比，60 mJ ESV可显著延缓异种移植瘤的生长，且对小鼠体重、肝肾功能均无显著影响。转录组分析显示，60 mJ ESV可抑制结直肠癌细胞增殖，并诱导细胞凋亡与铁死亡（ferroptosis）；上述结论通过免疫组织化学染色与蛋白质印迹实验得到了进一步验证。体外实验进一步揭示，ESV可通过激活p53信号通路，从机制层面抑制细胞增殖并诱导细胞凋亡与铁死亡。综上，60 mJ ESV可通过激活p53通路相关的增殖抑制与细胞死亡程序，显著抑制结直肠癌的生长。本研究结果提示，ESV疗法有望成为结直肠癌极具潜力的治疗策略。本数据集包含结直肠癌细胞系HT-29来源的异种移植瘤在60 mJ ESV治疗第15天时，对照组与60 mJ ESV处理组的RNA测序（RNA-Seq）转录组谱数据。