1.Influence of spleen preservation on hepatic fibrosis and relevant cytokine in rabbits with advanced schistosomiasis
Guisheng SHEN ; Jiasheng ZHU ; Guomin ZHU ; Youlong SHI ; Tianping WANG
Chinese Journal of Schistosomiasis Control 2009;21(6):491-495,插1
Objective To investigate the effects of spleen preservation on hepatic fibrosis and relevant cytokine in rabbits with advanced schistosomiasis. Methods After hepatic cirrhosis was induced by infecting Schistosoma japonicum cercariae in rabbits, total splenectomy (TSG), subtotal splenectomy (SSG) or sham operation (model control group, MCG) were performed respectively on these rabbits. Meanwhile,a normal control group (NCG) was established. The serum levels of tumor necrosis factor alpha (TNF-α) , interleukin-6 (IL-6) and interleukin-1 beta (IL-lβ) were detected respectively by radioimmunoassay(RIA) at the 8th, 15th and 21st week post-infection. The expressions of transforming growth factor betal (TGF-β1), type Ⅰ and type Ⅲ collagen in liver tissues were determined by immunohistochemistry before and after the operations. Results Compared with NCG, the serum levels of TNF-α, IL-6 and IL-1β of MCG rabbits increased significantly at the 8th week post-infection (P <0.01). However, the levels of them decreased to a lower level at the 15th week. At the 6th week after operation,no significant difference was found among the three model groups ( MCG, TSG, SSG) (P > 0.05). The expressions of TGF-β1, type Ⅰ and type Ⅲ collagen in liver tissue of MCG rabbits were significantly higher than those of NCG rabbits before the operation (P < 0. 01). No significant difference was found among the three model groups at the 6th week after the operation ( P > 0.05). Conclusion The residual splenic tissue after subtotal splenectomy does not aggravate the hepatic fibrosis at advanced schistosomiasis. The mechanism may be that the relevant cytokines of hepatic fibrosis (TGF-β1, TNF-a, IL-6, IL-1β) decreased to a lower level at this time,and splenectomy does not influence the levels of them.
2.Relationship between CD133 and chemoresistance in human gastric cancer and its associated mechanism.
Youlong ZHU ; Bojian JIANG ; Cheng CAI ; Shoulian WANG ; Jugang WU ; Jiwei YU
Chinese Journal of Gastrointestinal Surgery 2014;17(2):168-174
OBJECTIVETo explore the relationship between CD133(+) subsets cells in human gastric cancer (GC) and molecules of drug resistance and their sensitivity to 5-FU.
METHODSThree 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.
RESULTSExpressions 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).
CONCLUSIONSCD133 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.
AC133 Antigen ; ATP-Binding Cassette, Sub-Family B, Member 1 ; Antigens, CD ; metabolism ; Antineoplastic Agents ; pharmacology ; Apoptosis ; Cell Line, Tumor ; Drug Resistance, Neoplasm ; Fluorouracil ; Glycoproteins ; metabolism ; Humans ; Peptides ; metabolism ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; RNA, Small Interfering ; Stomach Neoplasms ; drug therapy ; metabolism ; pathology ; bcl-2-Associated X Protein