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

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 Plk1 can enhance the chemosensitization of LY294002. Thus, the gene therapy like targeted depletion of Plk1 may create new perspectives for chemosensitization of PC.

• Authors: Yonghuan Mao, Ling Xi, Quan Li, Sheng Wang, Zeling Cai, Xinhua Zhang, Chunzhao Yu
• Journal: Translational oncology (Transl Oncol) Vol. 11 Issue 4 Pg. 852-863 (Aug 2018) ISSN: 1936-5233 [Print] United States
• PMID: 29753186 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.