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Alkannin represses growth of pancreatic cancer cells based on the down regulation of miR-199a.

Authors
  • Zhang, Guochang1, 2
  • Zhai, Nan1
  • Zhang, Xiaofen1
  • 1 Department of Critical Care Medicine, Jining No.1 People's Hospital, Jining, Shandong, China. , (China)
  • 2 Affiliated Jining No. 1 People's Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, China. , (China)
Type
Published Article
Journal
BioFactors
Publisher
Wiley (John Wiley & Sons)
Publication Date
Sep 01, 2020
Volume
46
Issue
5
Pages
849–859
Identifiers
DOI: 10.1002/biof.1613
PMID: 31967380
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Alkannin displays tumor suppressive activity by initiating apoptosis. Here, we corroborated its role in pancreatic carcinoma (PANC-1) cells and addressed the molecular mechanism in which microRNA-199a (miR-199a) and Klotho might be implicated. PANC-1 and MIN6 cells were treated by alkannin and its role was evaluated in cellular viability. Next we assessed the ability of PANC-1 cells to proliferate, migrate, and invade as well as apoptosis process. Besides, proliferating cell nuclear antigen (PCNA), CyclinD1, p53, and caspases were quantified using Western blot. miR-199a was detected by qRT-PCR. miR-199a-silenced or -replenished cells were established to study its function role in Klotho in conjunction with alkannin. Further, Klotho-overexpressed or -silenced cells were constructed to investigate the alteration of mTOR and MEK/ERK pathways. Alkannin repressed the viability of PANC-1 cells instead of MIN6 cells. Alkannin counteracted the growth of PANC-1 cells through inhibiting proliferation, migration, and invasion and facilitating apoptosis, which was evidenced by the modulation on PCNA, CyclinD1, p53, and cleavage of caspases. The silence of miR-199a by alkannin was also involved in the antitumor process. Alkannin enhanced Klotho expression possibly through silencing miR-199a. Besides, mTOR and MEK/ERK signaling were counteracted by Klotho overexpression while facilitated by its silence. Alkannin inhibited the growth of PANC-1 cells via modulating miR-199a-Klotho node. During this process, mTOR and MEK/ERK pathways were blunted. © 2020 International Union of Biochemistry and Molecular Biology.

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