A quantitative method for measuring the antitumor potency of recombinant human endostatin in vivo.
Recombinant human endostatin (rhEndostatin) has been shown to inhibit tumor growth, but the variable antitumor activity of different rhEndostatin preparations has necessitated the development of an accurate, reproducible in vivo bioassay for evaluating the rhEndostatin activity. To assess the in vivo antitumor efficacy of rhEndostatin, H22 tumor-bearing mice received three doses of rhEndostatin and the potency of rhEndostatin preparations in inhibiting tumor growth was determined by ED(50)-potency assay and validated by dose-response parallel-line assay. There was a consistent and highly reproducible linear regression relationship between rhEndostatin dosage and tumor growth inhibition rate. The ED(50) values were determined from dose-response regression lines for seven rhEndostatin preparations with high reproducibility. On the basis of the current study, the potency of rhEndostatin preparations was assigned a value of 6.09 x 10(5) U/ampoule and a 95% confidence limit of 5.96 x 10(5)-6.22 x 10(5). We consider that this procedure can be served as a potential candidate pharmacopoeial method for potency measurement of different rhEndostatin preparations.
Xu
Ye-Fen
YF
Department of Biological Science and Technology and State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Mailbox 426, Nanjing University, 22 Hankou Road, Nanjing 210093, China.
Zhu
Li-Ping
LP
Hu
Bi
B
Rong
Zhi-Gang
ZG
Zhu
Hao-Wen
HW
Xu
Jia-Ming
JM
Wu
Zhi-Wei
ZW
Wang
Jian-Jun
JJ
Xu
Gen-Xing
GX
D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016001:Confidence Intervals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D043169:Endostatins / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D016014:Linear Models; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy*; D008297:Male; D051379:Mice; D010602:Pharmacopoeias as Topic; D011897:Random Allocation; D015203:Reproducibility of Results
D000970:Antineoplastic Agents; D043169:Endostatins