Antiangiogenic activities and cisplatin-combined antitumor activities of BPR0L075.
BACKGROUND
Antimitotic tubulin-binding BPR0L075 is structurally analogous to the vascular-disrupting combretastatin A-4.


METHODS
In vitro/in vivo models of endothelial cells cultures, Matrigel plug assay, tumor-bearing nude mice, and murine leukemia cells-inoculated mice were utilized to evaluate BPR0L075 for antiangiogenic and antitumoral activity spectra.


RESULTS
BPR0L075 concentration-dependently inhibited proliferation and migration of human umbilical vein endothelial cells (HUVECs), disrupted capillary tube formations of HUVECs and rat aorta endothelial cells, and suppressed in vivo VEGF-mediated angiogenesis in Matrigel plugs in mice. Besides inhibiting the colony growth of cancer cells, BPR0L075 suppressed growth of subcutaneously-xenografted human lung, colorectal, and cervical solid tumors in nude mice. Combination treatments of BPR0L075 plus cisplatin, compared to either agent alone, demonstrated a stronger growth inhibition against the tumor xenografts in nude mice and longer lifespan in the leukemia mice.


CONCLUSIONS
BPR0L075 is an antitumoral and antiangiogenic agent and potentiates the anticancer activity of cisplatin.
Chen
Ching-Ping
CP
Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli 35053, Taiwan, R.O.C.
Hu
Chih-Bo
CB
Yeh
Kai-Chia
KC
Song
Jen-Shin
JS
Yeh
Teng-Kuang
TK
Tung
Fei-Feng
FF
Hwang
Ling-Ling
LL
Tseng
Huan-Yi
HY
Huang
Yu-Chen
YC
Shy
Horng-Shing
HS
Hsieh
Su-Huei
SH
Shen
Chien-Chang
CC
Wang
Hsin-Sheng
HS
Hsieh
Hsing-Pang
HP
Liou
Jing-Ping
JP
Chao
Yu-Sheng
YS
Chen
Chiung-Tong
CT
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D048708:Cell Growth Processes / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D042783:Endothelial Cells / Q000187:drug effects; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D007941:Leukemia P388 / Q000188:drug therapy; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D023041:Xenograft Model Antitumor Assays
C488735:6-methoxy-3-(3',4',5'-trimethoxybenzoyl)-1H-indole; D020533:Angiogenesis Inhibitors; D007211:Indoles; D002945:Cisplatin