title: [Relationship between CD133 and chemoresistance in human gastric cancer and its associated mechanism].
abstract: OBJECTIVE
  To explore the relationship between CD133(+) subsets cells in human gastric cancer (GC) and molecules of drug resistance and their sensitivity to 5-FU.
  
  
  METHODS
  Three gastric cancer cell lines therein KATO-III(, SGC7901 and MKN45 were sorted by immunomagnetic beads cell sorting method. Then above cell lines were further divided into un-sorted GC cells, CD133(+) subgroup and CD133(-) subgroup. The expressions of CD133, P-gp, Bax and Bcl-2 were determined by RT-PCR, Western blot and immunoflurescence. Meanwhile, the sensitivity to 5-FU of three subgroups was detected by CCK-8 Kit. The apoptosis induced by 5-FU in three subgroups was determined by Hoechst 33258.
  
  
  RESULTS
  Expressions of CD133 in three CD133(+) subgroups were significantly higher than those in un-sorted GC cells and CD133(-) subgroup (all P<0.05). Expressions of P-gp and Bcl-2 in the three GC cell lines were different (all P<0.05). There were significant differences of expressions of P-gp, Bcl-2 and Bax among CD133(+) cells, un-sorted GC cells and CD133(-) cells (all P<0.05). CCK-8 detection showed that CD133(-) subgroup of MKN45 GC cell line was more sensitive than CD133(+) cells to 5-FU (P<0.05). Hoechst 33258 staining showed that there were more apoptotic cells in CD133(-) subgroup as compared to other two subgroups, and the least apoptotic cells were observed in CD133(+) subgroup of MKN45 GC cell line (P<0.05). CD133 sirna was transfected into MKN45 GC cell line and could down-regulate the expressions of CD133, P-gp, Bcl-2 and p-Akt, while the expression of Bax increased (all P<0.05).
  
  
  CONCLUSIONS
  CD133 may contribute to the resistance of GC cells to chemotherapy drug through P-gp, Bcl-2 and Bax. PI3K/Akt signal pathway may be involved in this process.
authors.affiliation: Department of General Surgery, The Third People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201999, China. jiweiyu919@hotmail.com.
authors.forename: Youlong
authors.initials: Y
authors.lastname: Zhu
authors.forename: Bojian
authors.initials: B
authors.lastname: Jiang
authors.forename: Cheng
authors.initials: C
authors.lastname: Cai
authors.forename: Shoulian
authors.initials: S
authors.lastname: Wang
authors.forename: Jugang
authors.initials: J
authors.lastname: Wu
authors.forename: Jiwei
authors.initials: J
authors.lastname: Yu
mesh_terms: D000071916:AC133 Antigen; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015703:Antigens, CD / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D010455:Peptides / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D051028:bcl-2-Associated X Protein
chemical_list: D000071916:AC133 Antigen; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015703:Antigens, CD; D000970:Antineoplastic Agents; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D034741:RNA, Small Interfering; D051028:bcl-2-Associated X Protein; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D005472:Fluorouracil