Combination of PI3K/Akt Pathway Inhibition and Plk1 Depletion Can Enhance Chemosensitivity to Gemcitabine in Pancreatic Carcinoma

Translational Oncology
Yonghuan MaoChunzhao Yu

Abstract

The prognosis of pancreatic cancer (PC) remains pessimistic because of the difficulty in early diagnosis as well as the little advance in chemotherapy. Although being the first-line chemotherapy drug for PC at present, gemcitabine still has some disadvantages, such as low drug sensitivity and significant side effects. Thus, how to further improve the sensitivity of PC cells to gemcitabine is still a difficult subject in the field of pancreatic cancer-treatment. Polo-like kinase 1 (Plk1) is closely related to poor outcome in many malignant tumors and its high expression is linked to chemoresistance in PC. As a downstream gene activated by PI3K/Akt signal pathway, we assumed that the targeted depletion of Plk1 could contribute to the chemosensitization induced by synergistic drug interaction of PI3K inhibitor LY294002 together with gemcitabine. To analyze effect of Plk1 in chemotherapy, we constructed two recombinant adenoviral vectors which carry enhanced green fluorescent protein (rAd-EGFP) and Plk1-shRNA (rAd-shPlk1), respectively. Both inhibition of PI3K/Akt signal pathway through PI3K inhibitor LY294002 and targeted depletion of Plk1 via recombinant adenoviral shRNA can cause chemosensitization, and the targeted depletion of...Continue Reading

Citations

Feb 5, 2019·Journal of Cellular Physiology·Lei Yue, Jing Guo
Jul 4, 2019·Proceedings of the National Academy of Sciences of the United States of America·Carolina TorresPaul J Grippo
Dec 23, 2020·Annals of Oncology : Official Journal of the European Society for Medical Oncology·H-Y YhimD-H Yang
Aug 4, 2021·Cancer Metastasis Reviews·Nianhong ChenPing Shi
Aug 30, 2021·Biochemical Pharmacology·Styliani IliakiInna S Afonina
Sep 7, 2021·Frontiers in Cell and Developmental Biology·Guangfu WangYi Miao

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Methods Mentioned

BETA
xenografts
PCR
Flow
flow cytometry
Assay
xenograft

Software Mentioned

GraphPad Prism
CellQuest
CompuSyn
SPSS
CalcuSyn

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AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.