Abstract：Objective To explore the effects and the mechanism of sulfated oligosaccharide phosphomannopentaose sulfate (PI-88) on invasion and migration of colon cancer SW620 cells.Methods Colon cancer SW620 cells were cultured and further divided into control group, solvent group and drug group. The cells in the control group were treated without any treatment, the cells in the drug group were treated with 0.5 mol/L PI-88 5μL, and the cells in the solvent group were treated with 5 μL PBS of equal volume. The cells of each group were cultured for 24 h after treatment. The migration distance of colon cancer SW620 cells were analyzed by wound healing assay. The number of migration and invasion of colon cancer SW620 cells were analyzed by Transwell assay. Finally, the protein expressions of heparanase(HPA), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor ( bFGF) in colon cancer SW620 cells were detected by Western blot assay.Results The data of wound healing assay showed that the migration distance of SW620 cells in the drug group(35.49±6.89)μm was less than that in the control group(216.75±21.43)μm and the solvent group(227.52±17.72)μm, and the difference was statistically significant(all P values ＜0.05).The data of Transwell assay showed that the number of migration(226±37) and invasion(89±11) of colon cancer SW620 cells in the drug group were less than those in the control group(875±93, 321±28) and the solvent group(843±116, 331±43), and the difference was statistically significant(all P values＜0.05). Moreover, the data of Western blot showed that the protein expressions of HPA,VEGF and bFGF in the drug group were decreased than those in the control group and the solvent group, and the differences were statistically significant(all P values＜0.05).Conclusions PI-88 inhibits colon cancer cell migration and invasion, the mechanism may be related to the inhibition of HPA, VEGF and bFGF protein expressions.
张磊, 吴慧丽, 肖兴国, 李琨琨, 张利, 张超. 硫酸寡糖复合物对人结肠癌SW620细胞迁移与侵袭能力的影响[J]. 中华解剖与临床杂志, 2018, 23(6): 543-547.
Zhang Lei, Wu Huili, Xiao Xingguo, Li Kunkun, Zhang Li, Zhang Chao.. Effect of sulfated oligosaccharide phosphomannopentaose sulfate on the migration and invasion of colon cancer SW620 cells. Chinese Journal of Anatomy and Clinics, 2018, 23(6): 543-547.
Global Burden of Disease Cancer Collaboration, Fitzmaurice C, Allen C, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the global burden of disease study[J].JAMA Oncol, 2017, 3(4): 524-548. DOI:10.1001/jamaoncol.2016.5688
[2]
Peng J, Li C, Wang F, et al. Right- and left-sided stage III colon cancers present different prognostic outcomes of oxaliplatin-based adjuvant chemotherapy after curative resection[J]. Cancer Manag Res, 2018, 10: 2095-2103. DOI:10.2147/CMAR.S163520
[3]
Bertelsen CA, Larsen HM, Neuenschwander AU, et al. Long-term functional outcome after right-sided complete mesocolic excision compared with conventional colon cancer surgery: a population-based questionnaire study[J]. Dis Colon Rectum, 2018, 61(9): 1063-1072. DOI:10.1097/DCR.0000000000001154
[4]
Liao BY, Wang Z, Hu J, et al. PI-88 inhibits postoperative recurrence of hepatocellular carcinoma via disrupting the surge of heparanase after liver resection[J]. Tumour Biol, 2016, 37(3): 2987-2998. DOI:10.1007/s13277-015-4085-8
[5]
Lewis KD, Robinson WA, Millward MJ, et al. A phase II study of the heparanase inhibitor PI-88 in patients with advanced melanoma[J]. Invest New Drugs, 2008, 26(1): 89-94. DOI:10.1007/s10637-007-9080-5
[6]
Raman K, Karuturi R, Swarup VP, et al. Discovery of novel sulfonated small molecules that inhibit vascular tube formation[J]. Bioorg Med Chem Lett, 2012, 22(13): 4467-4470. DOI: 10.1016/j.bmcl.2012.04.014
[7]
Khasraw M, Pavlakis N, McCowatt S, et al. Multicentre phase I/II study of PI-88, a heparanase inhibitor in combination with docetaxel in patients with metastatic castrate-resistant prostate cancer[J]. Ann Oncol, 2010, 21(6): 1302-1307. DOI: 10.1093/annonc/mdp524
[8]
Liu CJ, Chang J, Lee PH, et al. Adjuvant heparanase inhibitor PI-88 therapy for hepatocellular carcinoma recurrence[J]. World J Gastroenterol, 2014, 20(32): 11384-11393. DOI: 10.3748/wjg.v20.i32.11384
[9]
Rider CC, Mulloy B. Heparin, heparan sulphate and the TGF-β cytokine superfamily[J]. Molecules, 2017, 22(5) . pii: E713. DOI: 10.3390/molecules22050713
[10]
Bohdan N, Espín S, Águila S, et al. Heparanase activates antithrombin through the binding to its heparin binding site[J]. PLoS One, 2016, 11(6): e0157834. DOI: 10.1371/journal.pone.0157834
[11]
Poupard N, Badarou P, Fasani F, et al. Assessment of heparanase-mediated angiogenesis using microvascular endothelial cells: identification of λ-carrageenan derivative as a potent anti angiogenic agent[J]. Mar Drugs, 2017, 15(5) . pii: E134. DOI: 10.3390/md15050134
[12]
Song Y, Hu B, Qu H, et al. Novel 1, 3-N, O-Spiroheterocyclic compounds inhibit heparanase activity and enhance nedaplatin-induced cytotoxicity in cervical cancer cells[J]. Oncotarget, 2016, 7(24): 36154-36167. DOI: 10.18632/oncotarget.8959
[13]
Liu LP, Sheng XP, Shuai TK, et al. Helicobacter Pylori promotes invasion and metastasis of gastric cancer by enhancing heparanase expression[J]. World J Gastroenterol, 2018, 24(40): 4565-4577. DOI: 10.3748/wjg.v24.i40.4565
[14]
Jin H, Cui M. Gene silencing of heparanase results in suppression of invasion and migration of gallbladder carcinoma cells[J]. Biosci Biotechnol Biochem, 2018, 82(7): 1116-1122. DOI: 10.1080/09168451.2018.1456316
[15]
Hossain MM, Hosono-Fukao T, Tang R, et al. Direct detection of HSulf-1 and HSulf-2 activities on extracellular heparan sulfate and their inhibition by PI-88[J]. Glycobiology, 2010, 20(2): 175-186. DOI: 10.1093/glycob/cwp159
[16]
Hudachek SF, Eckhardt SG, Hicks B, et al. Population pharmacokinetic model of PI-88, a heparanase inhibitor[J]. Cancer Chemother Pharmacol, 2010, 65(4): 743-753. DOI: 10.1007/s00280-009-1080-z
[17]
Huang M, Huang B, Li G, et al. Apatinib affect VEGF-mediated cell proliferation, migration, invasion via blocking VEGFR2/RAF/MEK/ERK and PI3K/AKT pathways in cholangiocarcinoma cell[J]. BMC Gastroenterol, 2018, 18(1): 169. DOI: 10.1186/s12876-018-0870-3
[18]
Wang WM, Xu Y, Wang YH, et al. HOXB7 promotes tumor progression via bFGF-induced activation of MAPK/ERK pathway and indicated poor prognosis in hepatocellular carcinoma[J]. Oncotarget, 2017, 8(29): 47121-47135. DOI: 10.18632/oncotarget.17004
[19]
Liu L, Li C, Cochran S, et al. A focused sulfated glycoconjugate Ugi library for probing heparan sulfate-binding angiogenic growth factors[J]. Bioorg Med Chem Lett, 2012, 22(19): 6190-6194. DOI: 10.1016/j.bmcl.2012.08.001
2018, Vol. 23 
