摘要
This study aimed to observe the effects of tyroserleutide (tyrosyl-seryl-leucine, YSL) on the growth of human hepatocarcinoma BEL-7402 that was transplanted into nude mice, and explore its anti-tumor mechanism preliminarily. YSL, at doses of 80 μg·kg?1·d?1, 160 μg·kg?1·d?1 and 320 μg·kg?1·d?1 significantly inhibited the growth of the human hepatocarcinoma BEL-7402 tumor in nude mice, producing inhibition of 21.66%, 41.34%, and 34.78%, respectively. Ultra structure of BEL-7402 tumor in nude mice showed that YSL could induce tumor cells apoptosis and necrosis, cell organelle mitochondria and endoplasmic reticulum damage, and calcium over-load. By confocal laser scanning microscopy and flow cytometry, we found that 10 μg/mL YSL rapidly induced an increase of the concentration of cytoplasmic free calcium in BEL-7402 cells in vitro, and maintained high concentrations of cytoplasmic free calcium for 1 h. Then the calcium concentration began to decrease after 2 h, and was lower than that of the control group at 4 h and 24 h (p<0.05). YSL also decreased the mitochondrial transmembrane potential of BEL-7402 cells in vitro, but had no effect on the calcium homeostasis or mitochondrial transmembrane potential of Chang liver hepatocytes. So affecting calcium homeostasis, then inducing apoptosis and necrosis may be a mechanism by which YSL inhibits the tumor growth in animal model.
This study aimed to observe the effects of tyroserleutide (tyrosyl-seryl-leucine, YSL) on the growth of human hepatocarcinoma BEL-7402 that was transplanted into nude mice, and explore its anti-tumor mechanism preliminarily. YSL, at doses of 80 μg·kg?1·d?1, 160 μg·kg?1·d?1 and 320 μg·kg?1·d?1 significantly inhibited the growth of the human hepatocarcinoma BEL-7402 tumor in nude mice, producing inhibition of 21.66%, 41.34%, and 34.78%, respectively. Ultra structure of BEL-7402 tumor in nude mice showed that YSL could induce tumor cells apoptosis and necrosis, cell organelle mitochondria and endoplasmic reticulum damage, and calcium over-load. By confocal laser scanning microscopy and flow cytometry, we found that 10 μg/mL YSL rapidly induced an increase of the concentration of cytoplasmic free calcium in BEL-7402 cells in vitro, and maintained high concentrations of cytoplasmic free calcium for 1 h. Then the calcium concentration began to decrease after 2 h, and was lower than that of the control group at 4 h and 24 h (p<0.05). YSL also decreased the mitochondrial transmembrane potential of BEL-7402 cells in vitro, but had no effect on the calcium homeostasis or mitochondrial transmembrane potential of Chang liver hepatocytes. So affecting calcium homeostasis, then inducing apoptosis and necrosis may be a mechanism by which YSL inhibits the tumor growth in animal model.
作者
FU Zheng1, LU Rong2, LI Guoli1, ZHAO Lan1, GAO Weizhen3, CHE Xuchun1, JIAN Xu4, ZHOU Chunlei1 & YAO Zhi1 1. Department of Immunology, Tianjin Medical University, Tianjin 300070, China
2. Shenzhen Kangzhe Pharmaceutical Co. Ltd., Shenzhen, 518029, China
3. Department of Pharmacy, Tianjin Medical University, Tianjin 300070, China
4. Central Laboratory of Tianjin Medical University Hospital, Tianjin 300070, China
基金
This study was supported by the“863”Project(Grant No.2004AA2Z3170)from the Nat ional Important Project Grant(Grant No.03007)from the Ministry of Education of China
Pre-Explore of Key Basic Science Program of Ministry of Science and Technology ofChina(Grant No.2003CCA04300).
