Cui Changpeng, Xu Yinzhi, Xiong Xue, Aryal Uma K, Chen Andy, Chien Stanley, You Lidan, Li Baiyan, Yokota Hiroki
Department of Pharmacology, School of Pharmacy, Harbin Medical University, Harbin 150081, China.
Weldon School of Biomedical Engineering, Purdue University in Indianapolis, Indianapolis, IN 46202, USA.
Int J Mol Sci. 2025 Jan 25;26(3):1030. doi: 10.3390/ijms26031030.
Treating advanced metastatic cancer, particularly with bone metastasis, remains a significant challenge. In previous studies, induced tumor-suppressing (iTS) cells were successfully generated through genetic, chemical, and mechanical interventions. This study investigates the potential of electrical stimulation to generate iTS cells. Using a custom electrical stimulator with platinum electrodes, mesenchymal stem cells (MSCs) and Jurkat T cells were stimulated under optimized conditions (50 mV/cm, 10-100 Hz, 1 h). Conditioned medium (CM) from electrically stimulated cells demonstrated tumor-suppressing capabilities, inhibiting tumor cell migration, 3D spheroid growth, and cancer tissue fragment viability. Additionally, the CM reduced osteoclast maturation while promoting osteoblast differentiation. Proteomic analysis revealed enrichment of tumor-suppressing proteins, including histone H4, in the CM. Functional studies identified Piezo1 as a key mediator, as its knockdown significantly impaired the tumor-suppressive effects. Mechanistically, the process was distinct from other methods, such as mechanical vibration, with SUN1 inhibition showing no effect on iTS cell generation by electrical stimulation. These findings demonstrate the efficacy of electrical stimulation in enhancing the antitumor capabilities of MSCs and T cells, offering a novel approach to cancer therapy. Further exploration of this strategy could provide valuable insights into developing new treatments for metastatic cancer.
治疗晚期转移性癌症，尤其是伴有骨转移的癌症，仍然是一项重大挑战。在先前的研究中，通过基因、化学和机械干预成功生成了诱导肿瘤抑制（iTS）细胞。本研究调查了电刺激生成iTS细胞的潜力。使用带有铂电极的定制电刺激器，在优化条件（50 mV/cm，10 - 100 Hz，1小时）下刺激间充质干细胞（MSC）和Jurkat T细胞。电刺激细胞的条件培养基（CM）显示出肿瘤抑制能力，可抑制肿瘤细胞迁移、三维球体生长和癌组织碎片活力。此外，CM减少破骨细胞成熟，同时促进成骨细胞分化。蛋白质组学分析显示CM中富含包括组蛋白H4在内的肿瘤抑制蛋白。功能研究确定Piezo1为关键介质，因为其敲低显著损害肿瘤抑制作用。从机制上讲，该过程与其他方法（如机械振动）不同，抑制SUN1对电刺激生成iTS细胞没有影响。这些发现证明了电刺激在增强MSC和T细胞抗肿瘤能力方面的有效性，为癌症治疗提供了一种新方法。对该策略的进一步探索可为开发转移性癌症的新治疗方法提供有价值的见解。
