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Combinatorial Chemistry & High Throughput Screening

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ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

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Research Article

Apatinib Inhibits Bladder Cancer through Suppression of the VEGFR2- PI3K-AKT Signaling Pathway as Revealed by Network Pharmacology and in vitro Experimental Verification

Author(s): Weiwei Wang, Lin Chen*, Jin Yang*, Dandan Hu, Yafei Yang, Taotao Dong, Xiaoming Long, Yujian Zou, Jia Li, Xudong Ma, Wenbin Dai, Xin Zhou, Bo Chen and Yao Su

Volume 26, Issue 13, 2023

Published on: 22 March, 2023

Page: [2380 - 2392] Pages: 13

DOI: 10.2174/1386207326666230228101008

Price: $65

Abstract

Aims: This study aimed to evaluate the underlying pharmacological mechanisms of Apatinib anti-bladder cancer via network pharmacology and experimental verification.

Methods: Network pharmacology was used to screen the possible signaling pathways of Apatinib in bladder cancer, and the most likely pathway was selected for in vitro validation. CCK-8 and colony formation assay were used to detect the effect of Apatinib on the proliferation of bladder cancer cells. Hoechst staining and flow cytometry detected apoptosis of bladder cancer cells induced by Apatinib. Western blot was performed to distinguish the effect of Apatinib on the expression levels of key targets.

Results: Apatinib can affect many signaling pathways and the correlation of the PI3K-AKT signaling pathway was the greatest. In vitro experiments showed that Apatinib could inhibit bladder cancer cell proliferation, induce apoptosis, and up-regulate the expression of apoptosisrelated proteins Cleaved-PARP and down-regulate the expression of Bcl-2. Furthermore, Apatinib could decrease the protein expression of VEGFR2, P-VEGFR2, P-PI3K and P-AKT.

Conclusions: Apatinib could promote apoptosis of bladder cancer cells by inhibiting the VEGFR2- PI3K-AKT signaling pathway.

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