Experimental chemotherapy against xenografts derived from multidrug resistant KBv200 cells and parental drug-sensitive KB cells in nude mice by annonaceous acetogenin 89-2.
- Author:
Li-wu FU
1
;
Li-rong HE
;
Yong-ju LIANG
;
Li-ming CHEN
;
Hui-yu XIONG
;
Xiao-ping YANG
;
Qi-chao PAN
Author Information
- Publication Type:Journal Article
- MeSH: 4-Butyrolactone; analogs & derivatives; isolation & purification; pharmacology; ATP-Binding Cassette, Sub-Family B, Member 1; metabolism; Animals; Annona; chemistry; Antineoplastic Agents, Phytogenic; isolation & purification; therapeutic use; Cell Division; drug effects; Disease Models, Animal; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drugs, Chinese Herbal; isolation & purification; therapeutic use; Fatty Alcohols; isolation & purification; pharmacology; Humans; KB Cells; Male; Mice; Mice, Nude; Neoplasm Transplantation; Neoplasms, Experimental; drug therapy; Plants, Medicinal; chemistry; Xenograft Model Antitumor Assays
- From: Acta Pharmaceutica Sinica 2003;38(8):565-570
- CountryChina
- Language:English
-
Abstract:
AIMAnnonaceous acetogenin 89-2 was obtained from atemoya plant. To investigate the effect of 89-2 on experimental chemotherapy against xenografts derived from multidrug resistant KBv200 cells and parental drug-sensitive KB cells.
METHODSCytotoxicity was determined by tetrazolium (MTT) assay. The models of KB and KBv200 xenografts in nude mice were established to investigate the effect of 89-2 on experimental chemotherapy against cancer in vivo. Mechanistic experiments were conducted to examine the function of P-gp by Fura 2-AM assay.
RESULTSThe compound 89-2 showed potent cytotoxicity in KBv200 and KB cells, and the mean IC50 of 89-2 to KBv200 and KB cells was 48.7 and 64.6 nmol.L-1, respectively. The IC50 of 89-2 to multidrug resistant (MDR) cells was similar to that to the parental drug-sensitive cells (P < 0.05). In the models of KBv200 and KB cell xenografts in nude mice, 89-2 (0.90 mg.kg-1, q2d x 6) exhibited 52.3% and 56.5% in inhibiting the growth of xenografts, respectively. The toxicity was endurable. The intracellular accumulation of Fura-2 in KBv200 cells increased to 1.66, 2.03, and 2.74-fold, respectively, by addition of 12.8, 64 and 320 nmol.L-1 of 89-2.
CONCLUSIONBoth MDR KBv200 cells and parental drug-sensitive KB cells were sensitive to the treatment of 89-2 in vitro and in vivo. The mechanism of overcoming MDR was associated with the decrease of P-gp function MDR cells.
