Chen Lei, Yan Yang, Kong Fangen, Wang Jikai, Zeng Jia, Fang Zhen, Wang Zheyan, Liu Zhigang, Liu Fei
Department of Neurosurgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China.
The Cancer Center of the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China.
Cancers (Basel). 2022 Apr 18;14(8):2036. doi: 10.3390/cancers14082036.
To better understand the Ca overload mechanism of SDT killing gliomas, we examined the hypothesis that the early application of the mechanosensitive Ca channel Piezo1 antagonist (GsMTx4) could have a better anti-tumor effect.
The in vitro effect of low-energy SDT combined with GsMTx4 or agonist Yoda 1 on both the ROS-induced distribution of Ca as well as on the opening of Piezo1 and the dissociation and polymerization of the Ca lipid complex were assessed. The same groups were also studied to determine their effects on both tumor-bearing BALB/c-nude and C57BL/6 intracranial tumors, and their effects on the tumor-infiltrating macrophages were studied as well.
It was determined that ultrasound-activated Piezo1 contributes to the course of intracellular Ca overload, which mediates macrophages (M1 and M2) infiltrating under the oxidative stress caused by SDT. Moreover, we explored the effects of SDT based on the dissociation of the Ca lipid complex by inhibiting the expression of fatty acid binding protein 4 (FABP4). The Piezo1 channel was blocked early and combined with SDT treatment, recruited macrophages in the orthotopic transplantation glioma model.
SDT regulates intracellular Ca signals by upregulating Piezo1 leading to the inhibition of the energy supply from lipid and recruitment of macrophages. Therefore, intervening with the function of the Ca channel on the glioma cell membrane in advance is likely to be the key factor to obtain a better effect combined with SDT treatment.
为了更好地理解超声介导的肿瘤治疗（SDT）杀伤胶质瘤的钙超载机制，我们检验了以下假设：早期应用机械敏感钙通道Piezo1拮抗剂（GsMTx4）可能具有更好的抗肿瘤效果。
评估了低能量SDT联合GsMTx4或激动剂Yoda 1对活性氧诱导的钙分布、Piezo1开放以及钙脂质复合物解离和聚合的体外影响。还研究了相同组对荷瘤BALB/c裸鼠和C57BL/6颅内肿瘤的影响，以及它们对肿瘤浸润巨噬细胞的影响。
确定超声激活的Piezo1促成细胞内钙超载过程，该过程介导巨噬细胞（M1和M2）在SDT引起的氧化应激下浸润。此外，我们通过抑制脂肪酸结合蛋白4（FABP4）的表达，基于钙脂质复合物的解离探究了SDT的作用。早期阻断Piezo1通道并联合SDT治疗，在原位移植胶质瘤模型中募集巨噬细胞。
SDT通过上调Piezo1调节细胞内钙信号，导致脂质能量供应受抑制和巨噬细胞募集。因此，提前干预胶质瘤细胞膜上钙通道的功能可能是联合SDT治疗获得更好效果的关键因素。
