title: [Study on inhibitory effect of combined administration of bear bile powder and cyclophosphamide on colorectal cancer liver metastasis by regulating tumor microenvironment].
abstract: OBJECTIVE
  To explore the inhibitory effect of combined administration of bear bile powder (BBP) and cyclophosphamide (Cytoxan, CTX) on colorectal cancer liver metastasis by regulating tumor promotion inflammation microenvironment.
  
  
  METHODS
  The CRC liver metastasis mode in mice was established through in situ spleenic injection of SL4 tumor cells into spleens. The mice were randomly divided into 5 groups: the model group, the CTX (80 mg x kg(-1)) treatment group, the CTX + BBP high dose (300 mg x kg(-1)) group, the CTX + BBP middle dose (150 mg x kg(-1)) group and the CTX + BBP low dose (75 mg x kg(-1)) group. Mice were orally administered with drugs for 12 days, and sacrificed on the 13'h day for weighing their spleens and lives, HE staining, and immunofluorescence analysis. Their peripheral blood, and metastatic tumor in spleens and lives were analyzed with flow cytometry.
  
  
  RESULTS
  Spleen and liver weights of the: CTX treatment group and other doses groups were significantly lower than that of the model group. HE staining and immunofluorescence analysis showed that lymphocyte infiltration was detected in normal tissues, and macrophages infiltration was observed around the tumor tissues. Flow cytometry analysis showed that the number of T-lymphocytes in peripheral blood of different doses groups were much higher than that of the CTX treatment group (P < 0.05), with the rise in the ratio of CD4/CD8; the total number of lymphocytes in spleen cell suspension increased in different doses groups, compared to the CTX treatment group, with notable increase in B cells (P < 0.05) and significant decrease in CD11b, F4/80 cells (P < 0.05). The combined treatment showed less monocyte macrophages in liver metastasis than that of the CTX treatment group.
  
  
  CONCLUSIONS
  The combined treatment of bear bile powder and cyclophosphamide has the effect in not only protecting liver and increase immunity, but also in anti-inflammation and antitumor by regulating tumor microenvironment and reducing the collection of mononuclear macrophages. Particularly, the combined administration of low dose of bear bile powder and CTX shows the most significant effect in reducing inflammatory cell infiltration.
authors.affiliation: Beijing Anzhen Hospital Affiliated to Capital University of Medicine Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing 100029, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cui
authors.forename: Sa
authors.initials: S
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Lun
authors.initials: L
authors.lastname: Cai
authors.forename: Shu-Lan
authors.initials: SL
authors.lastname: Qiu
authors.forename: Jiao
authors.initials: J
authors.lastname: Zheng
authors.forename: Yan-Ju
authors.initials: YJ
authors.lastname: Miao
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Zhao
authors.forename: Jie
authors.initials: J
authors.lastname: Du
mesh_terms: D000818:Animals; D001646:Bile / Q000737:chemistry*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology / Q000556:secondary; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D059016:Tumor Microenvironment / Q000187:drug effects*; D001503:Ursidae
chemical_list: D003520:Cyclophosphamide