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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

Synergistic Cytotoxicity Effect of 5-Fluorouracil and SHP2 Inhibitor Demethylincisterol A3 on Cervical Cancer Cell

Author(s): Yang Liu, Hua Fu and Li Zuo*

Volume 22, Issue 7, 2022

Published on: 08 July, 2021

Page: [1313 - 1319] Pages: 7

DOI: 10.2174/1871520621666210708130703

Price: $65

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Abstract

Background: Demethylincisterol A3 (DTA3) has been identified as an SHP2 inhibitor and suppresses the growth of many cancer cells. 5-Fluorouracil (5-FU) is widely used for the clinical treatment of various cancers. However, the combination effects of 5-FU and DTA3 on cervical cancer cells remain unknown.

Objective: This study evaluates the mechanism of the combination effects of 5-FU and DTA3 in cervical cancer cells.

Methods: The synergistic cytotoxic effects of 5-FU and DTA3 in cervical cancer cells were calculated. Apoptosis was analysed by flow cytometry. Western blot analyses were used to examine the related signalling pathways.

Results: DTA3 and 5-FU synergized to induce apoptosis and repress proliferation of cervical cancer cells by downregulating the activation of PI3K/AKT and NF-κB signalling pathways. We provided evidence that the upregulation of SHP2 expression by transfection significantly inhibited the cytotoxicity of 5-FU and DTA3. SHP2 knockdown enhanced the anti-proliferation activity of 5-FU, indicating targeting SHP2 sensitized cervical cancer cells to 5-FU.

Conclusion: Our study demonstrates that SHP2 inhibitor DTA3 and 5-FU have a synergistic cytotoxic effect on cervical cancer cells. The synergistic combination of SHP2 inhibitor and 5-FU may present a promising strategy for the treatment of cervical cancer.

Keywords: Demethylincisterol A3, 5-fluorouracil, cervical cancer cells, synergy effects, SHP2, NF-κB.

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