title: Inositol Hexaphosphate and Inositol Inhibit Colorectal Cancer Metastasis to the Liver in BALB/c Mice.
abstract: Inositol hexaphosphate (IP6) and inositol (Ins), naturally occurring carbohydrates present in most mammals and plants, inhibit the growth of numerous cancers both in vitro and in vivo. In this study, we first examined the anti-metastatic effects of IP6 and Ins using a liver metastasis model of colorectal cancer (CRC) in BALB/c mice. CT-26 cells were injected into the splenic capsule of 48 BALB/c mice. The mice were then randomly divided into four groups: IP6, Ins, IP6 + Ins and normal saline control (n = 12 per group). IP6 and/or Ins (80 mg/kg each, 0.2 mL/day) were injected into the gastrointestinal tracts of the mice on the second day after surgery. All mice were sacrificed after 20 days, and the tumor inhibition rates were determined. The results demonstrated that the tumor weights of liver metastases and the tumor inhibition rates were reduced in the experimental groups compared to the control group and that treatment with the combination of IP6 and Ins resulted in greater inhibition of tumor growth than treatment with either compound alone. These findings suggest that IP6 and Ins prevent the development and metastatic progression of colorectal cancer to the liver in mice by altering expression of the extracellular matrix proteins collagen IV, fibronectin and laminin; the adhesion factor receptor integrin-β1; the proteolytic enzyme matrix metalloproteinase 9; and the angiogenic factors vascular endothelial growth factor, basic fibroblast growth factor, and transforming growth factor beta in the tumor metastasis microenvironment. In conclusion, IP6 and Ins inhibited the development and metastatic progression of colorectal cancer to the liver in BALB/c mice, and the effect of their combined application was significantly greater than the effect of either compound alone. This evidence supports further testing of the combined application of IP6 and Ins for the prevention of colorectal cancer metastasis to the liver in clinical studies.
authors.affiliation: Department of Public Health, Qingdao University Medical College, Qingdao 266021, China. bxfumin@163.com.
authors.forename: Min
authors.initials: M
authors.lastname: Fu
authors.affiliation: Department of Public Health, Qingdao University Medical College, Qingdao 266021, China. qdsongyang@126.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Song
authors.affiliation: School of Nursing, Qingdao University Medical College, Qingdao 266021, China. qdwenzhaoxia@126.com.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Wen
authors.affiliation: Basic Medical College, Qingdao University, Qingdao 266021, China. qdluxingyi@126.com.
authors.forename: Xingyi
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Public Health, Qingdao University Medical College, Qingdao 266021, China. qdlhcui@163.com.
authors.forename: Lianhua
authors.initials: L
authors.lastname: Cui
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control / Q000556:secondary; D000818:Animals; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000473:pathology*; D005260:Female; D007294:Inositol / Q000008:administration & dosage / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology / Q000556:secondary; D010833:Phytic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D011897:Random Allocation
chemical_list: D007294:Inositol; D010833:Phytic Acid
keywords: ECM; angiogenesis; inositol; inositol hexaphosphate; metastasis