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      Triptolide enhances the sensitivity of pancreatic cancer PANC-1 cells to gemcitabine by inhibiting TLR4/NF-κB signaling

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          Abstract

          Background: This study aimed to investigate roles of Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling in triptolide (TPL)-induced sensitivity of pancreatic cancer cells to gemcitabine (GEM). Methods: In vitro, pancreatic cancer PANC-1 cells were treated with lipopolysaccharide (LPS) to activate TLR4, TLR4-siRNA, GEM alone, or GEM plus TPL. In vivo, nude mice bearing PANC-1 cell xenografts were treated with GEM, TPL, or both. Cell proliferation was detected by MTT assay and Ki-67 staining. Apoptosis was assessed by flow cytometry and TUNEL assay. A double luciferase reporter gene was used to detect NF-κB activity. Results: The sensitivity of PANC-1 cells to GEM was reduced by LPS but enhanced by TLR4-siRNA. TPL inhibited expression of TLR4/NF-κB signaling components, which was reversed by LPS. The TPL+GEM group showed more apoptosis than the LPS+TPL+GEM group. Moreover, the activity of NF-κB and the expression of TLR4, p-p65 Survivin, CyclinD1 and Bcl-2 in the TPL+GEM group were lower than in the LPS+TPL+GEM group, whereas Bax expression was higher. The volume of transplanted tumors in the TPL+GEM group was lower than that in the TPL or GEM group. Phospho-p65, Survivin, CyclinD1 and Bcl-2 expression in transplanted tumors was lower in TPL+GEM group than in either single drug group. The Ki-67 staining score of the TPL+GEM group was lower and tumor cells apoptosis rate was increased when compared with TPL or GEM alone. Conclusions: TPL enhances the sensitivity of pancreatic cancer PANC-1 cells to GEM by inhibiting TLR4/NF-κB signaling.

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          Author and article information

          Journal
          Am J Transl Res
          Am J Transl Res
          ajtr
          American Journal of Translational Research
          e-Century Publishing Corporation
          1943-8141
          2019
          15 June 2019
          : 11
          : 6
          : 3750-3760
          Affiliations
          [1 ] Department of Gastroenterology, Huadong Hospital of Fudan University Shanghai 200338, China
          [2 ] Department of Gastroenterology, The First People’s Hospital of Lianyungang Lianyungang 222061, Jiangsu, China
          [3 ] Department of General Surgery, Ganyu District People’s Hospital of Lianyungang City Lianyungang 222100, Jiangsu, China
          [4 ] Department of Gastroenterology, Changhai Hospital of Second Military Medical University Shanghai 200433, China
          Author notes
          Address correspondence to: Xiao-Feng Yu, Department of Gastroenterology, Huadong Hospital of Fudan University, Shanghai 200338, China. Tel: +86-13472876295; Fax: +86-021-62483180; E-mail: yz_mjx@ 123456163.com
          [*]

          Equal contributors and co-first authors.

          Article
          PMC6614654 PMC6614654 6614654
          6614654
          31312385
          70513ed0-8050-4ea8-b8b5-7172bdd94933
          AJTR Copyright © 2019
          History
          : 07 October 2018
          : 30 March 2019
          Categories
          Original Article

          Triptolide,gemcitabine,pancreatic cancer,Toll-like receptor-4 protein,NF-κB

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