Zhu Zhitong, Jia Jing, Lu Rong, Lu Yi, Fu Zheng, Zhao Lan, Wang Li, Jin Mengjue, Zhao Lin, Gao Wenyuan, Yao Zhi
Department of Immunology, Tianjin Medical University, Tianjin 300070, China.
Int J Cancer. 2006 Mar 15;118(6):1539-44. doi: 10.1002/ijc.21501.
The tripeptide, tyroservatide (YSV), has been previously shown to have antitumor effects through unknown mechanism. In the current study, we examined whether YSV modulates the protumorigenic PI3K pathway in human BEL-7402 hepatocarcinoma cells. BEL-7402 hepatocarcinoma was transplanted into the subcutaneous tissues of nude mice, and YSV, at varying doses, was administered. RT-PCR and Western blot were used to analyze the expression of PTEN, AKT, p21 and p27. YSV at doses of 80 microg/kg/day, 160 microg/kg/day and 320 microg/kg/day markedly inhibited the growth of human BEL-7402 hepatocarcinoma (p < 0.05). YSV increased mRNA and protein expression of the tumor-suppressor genes, PTEN, p21 and p27, and inhibited the mRNA and protein expression of the oncogene AKT. Furthermore, YSV administration was associated with dephosphorylation of both PTEN (which activates PTEN) and AKT (which inhibits AKT). These results are consistent with the possibility that YSV mediates inhibition of tumor growth through inhibition of the PI3K pathway and suggests that YSV should be explored for use as an antitumor agent for hepatocarcinoma.
三肽酪丝缬肽（YSV）此前已被证明具有抗肿瘤作用，但其机制尚不清楚。在本研究中，我们检测了YSV是否能调节人BEL-7402肝癌细胞中促肿瘤的PI3K通路。将BEL-7402肝癌移植到裸鼠皮下组织，并给予不同剂量的YSV。采用RT-PCR和蛋白质印迹法分析PTEN、AKT、p21和p27的表达。剂量为80μg/kg/天、160μg/kg/天和320μg/kg/天的YSV显著抑制人BEL-7402肝癌的生长（p<0.05）。YSV增加了肿瘤抑制基因PTEN、p21和p27的mRNA和蛋白质表达，并抑制了癌基因AKT的mRNA和蛋白质表达。此外，给予YSV与PTEN（激活PTEN）和AKT（抑制AKT）的去磷酸化有关。这些结果与YSV通过抑制PI3K通路介导肿瘤生长抑制的可能性一致，并表明应探索将YSV用作肝癌抗肿瘤药物。
