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

سال انتشار: 1401
نوع سند: مقاله ژورنالی
زبان: انگلیسی
مشاهده: 250

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شناسه ملی سند علمی:

JR_IJBMS-25-4_015

تاریخ نمایه سازی: 25 اردیبهشت 1401

چکیده مقاله:

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 hENT۱. 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-۴۱۲۶. In this study, the anti-tumor effect and mechanism of a new derivative of gemcitabine named SZY-۲۰۰ on bladder cancer cells were investigated. SZY-۲۰۰ was assembled from the gemcitabine-lauric acid conjugate.Materials and Methods: Antiproliferative activities of SZY-۲۰۰ and lauric acid were evaluated using CCK-۸ assay and clonogenic survival assay. The hENT۱ inhibitor NBMPR was employed to determine the role of hENT۱ in the apoptotic activity of GEM, CP-۴۱۲۶, and SZY-۲۰۰. RT-qPCR, flow cytometry, fluorescence microscope, western blotting, and wound healing assay were used to study the mechanisms of SZY-۲۰۰. The target genes were predicted using the BATMAN-TCM database.Results: Our data showed that SZY-۲۰۰ could inhibit the proliferation of bladder cancer cells by inducing cell cycle arrest and apoptosis. The inhibitory effects were comparable to gemcitabine and CP-۴۱۲۶. SZY-۲۰۰ does not rely on hENT۱ to help it enter bladder cancer cells. Also, we found that lauric acid could inhibit the proliferation of bladder cancer cells. SZY-۲۰۰ could down-regulate the expressions of PPARG and PTGS۲ which were related to the occurrence and development of bladder cancer.Conclusion: SZY-۲۰۰ has the same or more advantages as CP-۴۱۲۶ and could be an ideal candidate drug for further in vivo investigation.

نویسندگان

Hongxia Wang

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai ۲۰۰۲۳۷, China

Zhiyu Shao

College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai ۲۰۱۶۲۰, China

Zhiwen Xu

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai ۲۰۰۲۳۷, China

Binghao Ye

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai ۲۰۰۲۳۷, China

Ming Li

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai ۲۰۰۲۳۷, China

Qiaoqiao Zheng

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai ۲۰۰۲۳۷, China

Xingyuan Ma

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai ۲۰۰۲۳۷, China

Ping Shi

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai ۲۰۰۲۳۷, China

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