Tripeptide tyroserleutide plus doxorubicin: therapeutic synergy and side effect attenuation.
BACKGROUND
Tripeptide tyroserleutide (YSL) is a novel small molecule anti-tumor polypeptide that has been shown to inhibit the growth of human liver cancer cells. In this study, we investigated the effects of YSL plus doxorubicin on the growth of human hepatocellular carcinoma BEL-7402 cells that had been transplanted into nude mice.


METHODS
Nude mice bearing human hepatocellular carcinoma BEL-7402 tumors were treated with successive intraperitoneal injections of saline; low-, mid-, or high-dose doxorubicin; or low-, mid-, or high-dose doxorubicin plus YSL. Effects on the weight and volume of the tumors were evaluated.


RESULTS
Co-administration of YSL and high-dose doxorubicin (6 mg/kg every other day) prolonged the survival time of tumor-bearing mice as compared to high-dose doxorubicin alone. As well, the anti-tumor effects of mid- and low-dose doxorubicin (2 and 0.7 mg/kg every other day, respectively) were enhanced when supplemented with YSL; the tumor growth inhibition rates for YSL plus doxorubicin were greater than the inhibition rates for the same dosages of doxorubicin alone. The combination of YSL and doxorubicin decreased chemotherapy-associated weight loss, leukocyte depression, and heart, liver, and kidney damage as compared to doxorubicin alone.


CONCLUSIONS
The combination of YSL plus doxorubicin enhances the anti-tumor effect and reduces the side effects associated with doxorubicin chemotherapy.
Zhu
Zhi-feng
ZF
Department of Immunology, Tianjin Medical University, Tianjin 300070, PR China. zhuzhifengcn@yahoo.com.cn
Chen
Li-juan
LJ
Lu
Rong
R
Jia
Jing
J
Liang
Yu
Y
Xu
Qiong
Q
Zhou
Chun-lei
CL
Wang
Li
L
Wang
Song
S
Yao
Zhi
Z
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D009842:Oligopeptides / Q000008:administration & dosage; D023041:Xenograft Model Antitumor Assays
D009842:Oligopeptides; D004317:Doxorubicin; C484773:H-Tyr-Ser-Leu-OH