In vitro anti-tumor effect of methotrexate modified by peptide.
- Author:
Ya-Mei ZHOU
1
;
Xue-Ping WU
;
Li ZENG
;
Ya-Rong ZHANG
;
Li-Jun PAN
;
Chi WANG
Author Information
1. College of Pharmacy, Chongqing University of Medical Sciences, Chongqing 400016, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Antimetabolites, Antineoplastic;
chemical synthesis;
pharmacology;
Apoptosis;
drug effects;
Bone Marrow Cells;
cytology;
Cell Cycle;
drug effects;
Cell Proliferation;
drug effects;
Cells, Cultured;
Drug Delivery Systems;
Gonadotropin-Releasing Hormone;
chemistry;
pharmacology;
Humans;
K562 Cells;
Leukocytes, Mononuclear;
MCF-7 Cells;
Methotrexate;
chemical synthesis;
pharmacology;
RNA, Messenger;
metabolism;
Rats;
Receptors, LHRH;
biosynthesis;
genetics
- From:
Acta Pharmaceutica Sinica
2012;47(4):452-458
- CountryChina
- Language:Chinese
-
Abstract:
This study is to investigate the anti-tumor effect in vitro of methotrexate modified by LH-RH peptide (LH-RH-MTX). LH-RH receptors highly expressing MCF-7 human breast carcinoma cell line and lowly expressing K562 human erythroleukemia cell line were served as the tested cells. The cell proliferation inhibition rates of LH-RH-MTX were detected by MTT colorimetric assay. The effects of LH-RH-MTX on the cell cycle and apoptosis rates were detected by flow cytometry. The inhibition rate of LH-RH-MTX on MCF-7 cells was much higher than that on K562 cells, and the inhibition rate of LH-RH-MTX on MCF-7 cells was much higher than that of free MTX at the same concentration. The inhibition rate of LH-RH-MTX on rat bone marrow mononuclear cells was less than that of free MTX. The number of MCF-7 cells in S phase increased after administration of LH-RH-MTX. The apoptosis rate of LH-RH-MTX group significantly increased compared with that of the control group and MTX group. The relative expression of LHRHR mRNA of LH-RH-MTX group markedly decreased compared with that of the control group and MTX group. LH-RH-MTX is realizable to reduce drug side effects, increase the therapeutic index and achieve tumor-targeted therapy.
