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Iranian Journal of Basic Medical Sciences

Iranian Journal of Basic Medical Sciences

IF: 2.1
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Antiproliferative and apoptotic activity of gemcitabine-lauric acid conjugate on human bladder cancer cells

Published:1 April 2022 DOI: 10.22038/IJBMS.2022.61118.13528
Hongxia Wang,?Zhiyu Shao,?Zhiwen Xu,?Binghao Ye,?Ming Li,?Qiaoqiao Zheng,?Xingyuan Ma,?P. Shi

Abstract

Objective(s): Gemcitabine is a first-line drug for the treatment of bladder cancer. One of the most important mechanisms of gemcitabine resistance is the low expression of cellular membrane transporter hENT1. Various derivatives containing fatty acid side chains have been developed in order to facilitate gemcitabine uptake and prolong its retention in cells, such as CP-4126. In this study, the anti-tumor effect and mechanism of a new derivative of gemcitabine named SZY-200 on bladder cancer cells were investigated. SZY-200 was assembled from the gemcitabine-lauric acid conjugate. Materials and Methods: Antiproliferative activities of SZY-200 and lauric acid were evaluated using CCK-8 assay and clonogenic survival assay. The hENT1 inhibitor NBMPR was employed to determine the role of hENT1 in the apoptotic activity of GEM, CP-4126, and SZY-200. RT-qPCR, flow cytometry, fluorescence microscope, western blotting, and wound healing assay were used to study the mechanisms of SZY-200. The target genes were predicted using the BATMAN-TCM database. Results: Our data showed that SZY-200 could inhibit the proliferation of bladder cancer cells by inducing cell cycle arrest and apoptosis. The inhibitory effects were comparable to gemcitabine and CP-4126. SZY-200 does not rely on hENT1 to help it enter bladder cancer cells. Also, we found that lauric acid could inhibit the proliferation of bladder cancer cells. SZY-200 could down-regulate the expressions of PPARG and PTGS2 which were related to the occurrence and development of bladder cancer. Conclusion: SZY-200 has the same or more advantages as CP-4126 and could be an ideal candidate drug for further in vivo investigation.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
S-(4-NITROBENZYL)-6-THIOINOSINE 38048-32-7 C17H17N5O6S 124 suppliers $15.00-$1871.10
S-(4-NITROBENZYL)-6-THIOINOSINE 38048-32-7 C17H17N5O6S 124 suppliers $15.00-$1871.10
S-(4-NITROBENZYL)-6-THIOINOSINE 38048-32-7 C17H17N5O6S 124 suppliers $15.00-$1871.10
S-(4-NITROBENZYL)-6-THIOINOSINE 38048-32-7 C17H17N5O6S 124 suppliers $15.00-$1871.10

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