Abstract:Objective To explore the mechanism of polysaccharide purified from Bacillus Calmette-Guerin (BCG) formulation on proliferation and anti-apoptosis of pancreatic cancer cell lines. Methods The inhibitory effect of polysaccharide purified from BCG formulation on cell growth of pancreatic cancer cell line PANC-1, SW1990 and primary cells was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Flow cytometry was used to detect the cell apoptosis rates. Results The inhibitory rates of PANC-1, SW1990 and primary cell proliferation were respectively (9.53±0.82)%, (10.02±0.95)%, (9.08±0.78)% in the high-concentration group of purified polysaccharide from BCG formulation, (8.84±0.77)%, (9.62±0.95)%, (8.18±0.71)% in the medium-concentration group, and (5.72±0.48)%, (6.48±0.48)%, (5.06±0.44)% in the low-concentration group, which were all significantly higher than those of the blank control group ((3.92±0.28)%, (4.72±0.40)%, (2.91±0.26)%) and BCG-polysaccharide nucleic acid group ((4.82±0.48)%, (5.46±0.46)%, (4.22±0.38)%). The inhibitory rates of PANC-1, SW1990 and primary cell proliferation in the group of purified polysaccharide combined with gemcitabine (GEM) were (16.54±1.56)%, (18.28±1.86)% and (15.88±1.92)% respectively, which were superior to those of GEM or purified polysaccharide alone group as well as those of BCG-polysaccharide nucleic acid plus GEM group ((13.82±1.42)%, (14.88±1.72)%, (12.32±1.18)%), with statistically significant differences (all P<0.05). The apoptosis rates of PANC-1, SW1990 and primary cell proliferation were significantly higher in the groups of high-, medium- and low-concentration of purified polysaccharide than in the blank control group and BCG-polysaccharide nucleic acid group. The apoptosis rates of PANC-1, SW1990 and primary cell in the group of purified polysaccharide combined with GEM were superior to those of GEM or purified polysaccharide alone group as well as those of BCG-polysaccharide nucleic acid plus GEM group, showing statistically significant differences (all P<0.05). Conclusions The purified polysaccharide from BCG formulation has an anti-tumor effect prevailing against that of BCG-polysaccharide nucleic acid. The efficacy is more remarkable when it is combined with GEM.
[1] Jiang J,Yu C,Chen M,et al.Reduction of miR-29c enhances pancreatic cancer cell migration and stem cell-like phenotype[J].Oncotarget,2014,5(6):2767-2778. [2] Chen W,Zheng R,Baade PD,et al. Cancer statistics in China, 2015 [J]. CA Cancer J Clin,2016,66(2):115-132. [3] Salman B,Zhou D,Jaffee EM,et al. Vaccine therapy for pancreatic cancer[J]. Oncoimmunology,2013,2(12):e26662. [4]赵江桥,薛芝敏,杨佳平,等.胰腺癌相关危险因素的病例对照研究[J].现代肿瘤医学,2018,26(8):1229-1232. [5] 高戈,高梓博,高洁生.卡介菌复合多糖及其制备方法和用途[P].中国,ZL 201310262024.X,2015.9.30. [6]Lin QJ,Yang F,Jin C,et al. Current status and progress of pancreatic cancer in China [J]. World J Gastroenterol,2015,21(26):7988-8003. [7] Xu Z,Pothula SP,Wilson JS,et al. Pancreatic cancer and its stroma:a conspiracy theory[J]. World J Gastroenterol,2014,20(32):11216-11229. [8] Halbrook CJ, Lyssiotis CA. Employing metabolism to improve the diagnosis and treatment of pancreatic cancer [J]. Cancer Cell, 2017, 31(1):5-19. [9] Shukla SK, Purohit V, Mehla K, et al. MUC1 and HIF-1alpha signaling crosstalk induces anabolic glucose metabolism to impart gemcitabine resistance to pancreatic cancer [J]. Cancer Cell, 2017, 32(3):392. [10] McDonald OG, LiX, Saunders T, et al. Epigenomic reprogramming during pancreatic cancer progression links anabolic glucose metabolism to distant metastasis [J]. Nat Genet, 2017, 49(3):367-376.