Inhibition of Regulatory Volume Decrease Enhances the Cytocidal Effect of Hypotonic Shock in Hepatocellular Carcinoma.
Inhibition of Regulatory Volume Decrease Enhances the Cytocidal Effect of Hypotonic Shock in Hepatocellular Carcinoma.
复制标题
调节体积的抑制减少会增强肝细胞癌中低渗性休克的胞质效应。
DOI：
10.7150/jca.15181
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发表时间：
2016
影响因子：
3.9
通讯作者：
Otsuji E
中科院分区：
文献类型：
--
作者：
Kudou M;Shiozaki A;Kosuga T;Ichikawa D;Konishi H;Morimura R;Komatsu S;Ikoma H;Fujiwara H;Okamoto K;Hosogi S;Nakahari T;Marunaka Y;Otsuji E
背景：低渗休克通过细胞破裂诱导细胞杀伤作用，基于这一机制的肿瘤治疗已被临床应用于肝癌患者。我们在此研究低渗休克联合抑制调节性体积减少作为肝癌治疗的有效性。方法：在连接高速数码摄像机的差示干涉对比显微镜下观察人肝癌细胞系的形态学变化。使用高分辨率流式细胞仪观察使用或不使用氯、钾或水通道阻滞剂时低渗休克下细胞体积的变化。为了研究细胞杀伤作用，比较了在低渗溶液中使用和不使用每种通道阻滞剂后存活细胞的数量（再孵育实验）。结果：录像显示细胞在蒸馏水作用下迅速膨胀并破裂。细胞体积测量显示，在轻度低渗休克下，调节体积减少，而严重低渗休克导致细胞破裂，碎片数量增加。此外，每种通道阻滞剂都抑制了细胞的调节体积减少。再孵育实验表明，低渗休克对暴露于低渗溶液中的细胞有杀细胞作用，并且每种通道阻滞剂的额外处理增强了这些作用。结论：氯离子阻滞剂、钾离子阻滞剂或水通道阻滞剂抑制低渗休克对肝癌细胞的杀伤作用增强。低渗休克联合抑制调节性体积减少比单独低渗休克更有效。
Background: Hypotonic shock induces cytocidal effects through cell rupture, and cancer therapy based on this mechanism has been clinically administered to hepatocellular carcinoma patients. We herein investigated the effectiveness of hypotonic shock combined with the inhibition of regulatory volume decrease as cancer therapy for hepatocellular carcinoma. Methods: Morphological changes in human hepatocellular carcinoma cell lines were observed under a differential interference contrast microscope connected to a high-speed digital video camera. Cell volume changes under hypotonic shock with or without chloride, potassium, or water channel blockers were observed using a high-resolution flow cytometer. In order to investigate cytocidal effects, the number of surviving cells was compared after exposure to hypotonic solution with and without each channel blocker (re-incubation experiment). Results: Video recordings showed that cells exposed to distilled water rapidly swelled and then ruptured. Cell volume measurements revealed regulatory volume decrease under mild hypotonic shock, whereas severe hypotonic shock increased the number of broken fragments as a result of cell rupture. Moreover, regulatory volume decrease was inhibited in cells treated with each channel blocker. Re-incubation experiments showed the cytocidal effects of hypotonic shock in cells exposed to hypotonic solution, and additional treatments with each channel blocker enhanced these effects. Conclusion: The inhibition of regulatory volume decrease with chloride, potassium, or water channel blockers may enhance the cytocidal effects of hypotonic shock in hepatocellular carcinoma. Hypotonic shock combined with the inhibition of regulatory volume decrease was a more effective therapy than hypotonic shock alone.