Background: This study aimed to investigate roles of Toll-like receptor 4 (TLR4)/nuclear factor (NF)-kappa B 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-kappa B 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-kappa B 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-kappa B 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-kappa B signaling.
[1]Fudan Univ, Huadong Hosp, Dept Gastroenterol, Shanghai 200338, Peoples R China;
[2]First Peoples Hosp Lianyungang, Dept Gastroenterol, Lianyungang 222061, Jiangsu, Peoples R China;
[3]Ganyu Dist Peoples Hosp Lianyungang City, Dept Gen Surg, Lianyungang 222100, Peoples R China;
[4]Second Mil Med Univ, Changhai Hosp, Dept Gastroenterol, Shanghai 200433, Peoples R China
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