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目前寻找有效的药物仍是治疗肿瘤的关键环节之一.酪丝亮肽为中国新近研发并具有自主知识产权的三肽化合物.观察了酪丝亮肽的抗肝癌作用,并研究了其对肿瘤细胞钙稳态的影响,以初步探讨它的抗肿瘤作用机制.结果发现,酪丝亮肽能显著抑制人肝癌BEL-7402裸鼠移植瘤的生长,160μg/(kg·d)治疗组肿瘤生长抑制率可达41.34%,电子显微镜观察发现酪丝亮肽可引起移植瘤细胞的坏死和凋亡,细胞器线粒体和内质网损伤,并出现钙沉积.应用激光扫描共聚焦显微镜及流式细胞仪观察发现,10μg/mL酪丝亮肽在400s内可引起体外培养BEL-7402细胞胞浆钙离子浓度迅速升高,最高幅度可达239.13%;持续作用1h后BEL-7402胞浆钙离子维持在高水平,作用2h后胞浆钙离子浓度开始下降,4和24h时的胞浆钙离子水平均低于对照,相同剂量的药物对人正常肝细胞株Chang氏肝无明显影响;酪丝亮肽还可使体外培养的BEL-7402细胞线粒体跨膜电位明显下降,提示其抗肝癌机制可能是通过影响肿瘤细胞的钙稳态,诱导其发生坏死或凋亡.
At present, the search for effective drugs is still one of the key steps in the treatment of cancer.Tetrometrine is a newly developed tripeptide compound with independent intellectual property rights in China.It has been observed that tyroserpin exerts its anti-hepatocarcinoma effect and its effect on tumor Cell calcium homeostasis in vitro.It was found that the tyroserpin could significantly inhibit the growth of human hepatocellular carcinoma BEL-7402 xenografts in nude mice, and the tumor growth in the treatment group of 160μg / (kg · d) The inhibition rate could reach 41.34%. Electron microscopy showed that tyroserpin could induce the necrosis and apoptosis of transplanted tumor cells, the mitochondria and endoplasmic reticulum of organelle, and the calcium deposition.Application of laser scanning confocal microscopy and flow cytometry The results showed that the cytosolic calcium concentration of BEL-7402 cells increased rapidly at the highest level of 239.13% after treated with 10μg / mL of tyroserulene in 400s. The cytosolic calcium of BEL-7402 cells maintained at High levels of cytosolic calcium began to decline after 2h, 4 and 24h cytosolic calcium levels were lower than the control, the same dose of drug on human normal liver cell Chang’s liver had no significant effect; tyroserpin Can also make in vitro Cultured BEL-7402 cells mitochondrial transmembrane potential decreased significantly, suggesting that its mechanism of anti-liver cancer may be affected by the tumor cell calcium homeostasis, induction of necrosis or apoptosis.