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

[ Vol. 22 , Issue. 7 ]

Author(s):

Yang Liu, Hua Fu and Li Zuo*   Pages 1313 - 1319 ( 7 )

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

Affiliation:

Department of Immunology, Guizhou Medical University, Guiyang, Guizhou, CN 550004, Department of Gastroenterology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, CN 550004, Department of Immunology, Guizhou Medical University, Guiyang, Guizhou, CN 550004

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