[In vitro anti-tumor effect of methotrexate modified by peptide].
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.
College of Pharmacy, Chongqing University of Medical Sciences, Chongqing 400016, China.
Ya-Mei
YM
Zhou
Xue-Ping
XP
Wu
Li
L
Zeng
Ya-Rong
YR
Zhang
Li-Jun
LJ
Pan
Chi
C
Wang
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D016503:Drug Delivery Systems; D007987:Gonadotropin-Releasing Hormone / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020014:K562 Cells; D007963:Leukocytes, Mononuclear; D061986:MCF-7 Cells; D008727:Methotrexate / Q000138:chemical synthesis / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011966:Receptors, LHRH / Q000096:biosynthesis* / Q000235:genetics
D000964:Antimetabolites, Antineoplastic; D012333:RNA, Messenger; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D008727:Methotrexate