Natural compound Oblongifolin C confers gemcitabine resistance in pancreatic cancer by downregulating Src/MAPK/ERK pathways

Cell Death & Disease
Yang LiHongxi Xu

Abstract

Gemcitabine (GEM)-induced drug resistance is the major reason for the failure of chemotherapy in pancreatic cancer (PC). In this study, we found that Oblongifolin C (OC) efficiently inhibited PC cell proliferation by inducing G0/G1 arrest and apoptosis. Also, our mechanism study demonstrated that OC re-sensitized the GEM-resistant PC cells through the ubiquitin-proteasome-dependent degradation of Src, and then downregulating the MAPK pathway. Knockdown of Src plus OC resulted in a greater inhibitory effect in GEM-resistant PC cells. In contrast, Src overexpression reversed OC-mediated chemosensitization, thereby implicating Src in the action of OC. Moreover, our in vivo study showed that OC suppressed the tumor growth via the downregulation of Src, and enhanced the chemosensitivity of GEM-resistant PC to GEM. Overall, our results have revealed that OC is applicable as a promising agent for overcoming GEM-resistant PC, especially with aberrant Src expression.

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Citations

Dec 9, 2020·International Journal of Biological Macromolecules·Yuping ZhaoHafiz M N Iqbal
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jiling FengHongxi Xu
Aug 28, 2021·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Abdullah ShopitXiaohong Shu
Sep 30, 2021·Natural Products and Bioprospecting·Christian Bailly, Gérard Vergoten
Oct 14, 2021·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·J WeiY Ding

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Methods Mentioned

BETA
confocal microscopy
flow cytometry
transfection
ubiquitination
immunoprecipitation
xenograft
PCR

Software Mentioned

FlowJo
SPSS
GraphPad Prism

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