Anti-tumor effects and cell motility inhibition of the DN604-gemcitabine combined treatment in human bladder cancer models.

Szczegóły
Abstrakt

Tytuł:: Anti-tumor effects and cell motility inhibition of the DN604-gemcitabine combined treatment in human bladder cancer models.
Autorzy:: Wang X; Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China.
Chen F; Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China; Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research, Southeast University, Nanjing 211189, China.
Gou S; Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China; Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research, Southeast University, Nanjing 211189, China. Electronic address: .
Źródło:: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2021 Jan 01; Vol. 29, pp. 115858. Date of Electronic Publication: 2020 Nov 07.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Publication: Oxford : Elsevier Science
Original Publication: Oxford : New York : Pergamon Press, c1993-
MeSH Terms:: Antineoplastic Combined Chemotherapy Protocols/*pharmacology
Carboplatin/*analogs & derivatives
Deoxycytidine/*analogs & derivatives
Urinary Bladder Neoplasms/*drug therapy
Animals ; Antineoplastic Combined Chemotherapy Protocols/chemical synthesis ; Antineoplastic Combined Chemotherapy Protocols/chemistry ; Apoptosis/drug effects ; Carboplatin/chemistry ; Carboplatin/pharmacology ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Deoxycytidine/chemistry ; Deoxycytidine/pharmacology ; Dose-Response Relationship, Drug ; Drug Screening Assays, Antitumor ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Molecular Structure ; Neoplasms, Experimental/drug therapy ; Neoplasms, Experimental/metabolism ; Neoplasms, Experimental/pathology ; Structure-Activity Relationship ; Tumor Cells, Cultured ; Urinary Bladder Neoplasms/metabolism ; Urinary Bladder Neoplasms/pathology ; Gemcitabine
Contributed Indexing:: Keywords: Bladder cancer; Cell motility; Combined treatment; Pt(II) compound
Substance Nomenclature:: 0 (DN604)
0W860991D6 (Deoxycytidine)
BG3F62OND5 (Carboplatin)
0 (Gemcitabine)
Entry Date(s):: Date Created: 20201121 Date Completed: 20210730 Latest Revision: 20221207
Update Code:: 20240105
DOI:: 10.1016/j.bmc.2020.115858
PMID:: 33218897
: Czasopismo naukowe

Full Text Finder

Bladder cancer is one of the major tumors for men in the world, in which therapy the combination of cisplatin and gemcitabine is still fist-line applied to treat with advanced or metastatic bladder cancer. In our early study, we developed a potential Pt(II) agent, DN604, which has anti-tumor effect as potent as cisplatin toward bladder cancers. Herein, we aim at investigating the combinatory application of DN604 with gemcitabine for bladder cancer treatment. In vitro studies proved that the combined treatment of DN604 and gemcitabine could limit cell proliferation by elevating the incidence of DNA damage induced apoptosis. Notably, further researches showed that the DN604-gemcitabine treatment suppressed cell autophagy to inhibit cell motility upon the ROS dependent p38 MAPK signaling pathway, explicating its better anti-tumor activity than single drug treatment or the cisplatin-gemcitabine treatment. In vivo tests confirmed that the DN604-gemcitabine treatment has superior anti-tumor activity with low toxicity to cisplatin or its combination with gemcitabine treatments. DN604 plus gemcitabine, is of great significance for the treatment with human bladder cancer. Our study has provided a potential combination treatment option.
(Copyright © 2020 Elsevier Ltd. All rights reserved.)

Informacja