Regulation of cell apoptosis and proliferation in pancreatic cancer through PI3K/Akt pathway via Polo-like kinase 1

Mao,Yonghuan; Xi,Ling; Li,Quan; Cai,Zeling; Lai,Yimei; Zhang,Xinhua; Yu,Chunzhao

doi:10.3892/or.2016.4820

Regulation of cell apoptosis and proliferation in pancreatic cancer through PI3K/Akt pathway via Polo-like kinase 1

Authors:
- Yonghuan Mao
- Ling Xi
- Quan Li
- Zeling Cai
- Yimei Lai
- Xinhua Zhang
- Chunzhao Yu
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Affiliations: Department of General Surgery, The Second Clinical Medical School of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Gerontology, The First Clinical Medical School of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Pathology, The First Clinical Medical School of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Pediatric Medicine, Jiangsu Province Hospital, Nanjing, Jiangsu 210029, P.R. China
Published online on: May 18, 2016 https://doi.org/10.3892/or.2016.4820
Pages: 49-56
Copyright: © Mao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pancreatic cancer has a poor prognosis. It is reported that the PI3K/Akt pathway is activated in many cancers, and inhibition of the PI3K/Akt pathway can induce cell apoptosis in most cancers. Polo-like kinase 1 (Plk1) is also overexpressed in most malignancies, and it controls multiple aspects of mitosis and apoptosis. Previous studies identified that PI3K/Akt-dependent phosphorylation of Plk1-Ser99 is required for metaphase-anaphase transition. In this study, we aimed to investigate the molecular mechanism of PI3K/Akt pathway regulating cell proliferation and apoptosis in pancreatic cancer cell lines (AsPC-1, BxPC-3, PANC-1). Immunohistochemistry (IHC) was used to assess Akt levels in human pancreatic tissues and pancreatic cancer tissues. MTT assay was used to detect cell proliferation. The mRNA was quantified by quantitative reverse transcription-PCR. Western blot analysis was used to detect the protein levels of p-Akt, Akt, Plk1, BAX, Bcl-2, XIAP, cleaved caspase-3 and caspase-3. Recombinant adenovirus vector containing Plk1-shRNA was constructed to inhibit Plk1 expression. Cell apoptosis was detected by flow cytometry and the apoptosis of tumor xenograft was assessed by TUNEL assay. The study showed that inhibition of PI3K/Akt pathway can induce cell apoptosis and reduce cell proliferation by downregulating Plk1 in vitro and in vivo. Additionally, Plk1 inhibition can lead to cancer cell apoptosis through inactivating XIAP, activating caspase-3, upregulating BAX and downregulating Bcl-2. Therefore, this study provided the molecular mechanism of PI3K/Akt pathway and Plk1 in the pancreatic cancer cell proliferation and apoptosis, which may benefit for the therapy of pancreatic cancer.

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