A Conjugate of Methotrexate and an Analog of Luteinizing Hormone Releasing Hormone Shows Increased Efficacy Against Prostate Cancer

Overview

Journal Sci Rep

Specialty Science

Date 2016 Sep 23

PMID 27654169

Citations 12

Authors

Shengsheng Zhu

Qinxia Wang

Juan Jiang

Yongwei Luo

Zuyue Sun

Affiliations

Soon will be listed here.

Abstract

LHRH receptor, is over-expressed in a variety of human tumors and, is a potential binding site for targeted metastatic prostate cancer therapy. The objectives of our study were to synthesize a bioconjugate of the LHRH analog [DLys]-LHRH and the anti-tumor agent methotrexate and test the hypothesis that [DLys]-LHRH-MTX targets and inhibits prostate cancer cell growth in vitro and in vivo. The results of in vitro studies, showed that both [DLys]-LHRH-MTX and MTX displayed superior cytotoxicity against prostate cancer cells in a concentration-dependent manners, with IC concentrations for PC-3 cells of, 1.02 ± 0.18 μmol/L and 6.34 ± 1.01 μmol/L; for DU-145 cells, 1.53 ± 0.27 μmol/L and 8.03 ± 1.29 μmol/L; and for LNCaP cells, 1.93 ± 0.19 μmol/L and 9.68 ± 1.24 μmol/L, respectively. The IC values of [DLys]-LHRH-MTX and MTX were 110.77 ± 15.31 μmol/L and 42.33 ± 7.25 μmol/L, respectively. Finally, [DLys]-LHRH-MTX significantly improved the anti-tumor activity of MTX in nude mice bearing PC-3 tumor xenografts. The inhibition ratios of tumor volume and tumor weight in the [DLys]-LHRH-MTX treated group were significantly higher than those in the MTX-treated group. Tumor volume doubling time was also significantly extended from 6.13 days in control animals to 9.67 days in mice treated with [DLys]-LHRH-MTX. In conclusion, [DLys]-LHRH -MTX may be useful in treating prostate cancer.

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