title: Tumor inhibition effects and mechanisms of Angelica sinensis and Sophorae flavescentis ait decoction combined with cisplatin in xenograft mice.
abstract: BACKGROUND
  To investigate tumor inhibition effects and mechanisms of Angelica sinensis and Sophorae flavescentis ait decoction (ASSF) combined with diamine-dichloroplatinum (DDP).
  
  
  METHODS
  Bodyweight, tumor inhibition rate and q value were calculated for single ASSF or ASSF combined with DDP on H22 carcinoma xenograft KM mice. Biochemical methods for serum LDH, AST, ALT, and AKP, ELISA method for serum HIF-1α, pathological assessemnt of thymus, immunohistochemistry detection of tumor tissue caspase3 and mutant p53 protein, and qRT-PCR detection of bax/ bcl-2 mRNA were applied.
  
  
  RESULTS
  Compared with DDP control group, the bodyweight increased in ASSF-DDP group (p<0.01). Tumor inhibition rates for DDP, ASSF, ASSF-DDP were 62.7%. 43.7% and 71.0% respectively, with a q value of 0.90. Compared with other groups, thymus of DDP control group had obvious pathological injury (p<0.01), serum LDH, AST, ALT, AKP increased significantly in DDP control group (p<0.01), while serum HIF-1α was increased in the model control group. Compared with this latter, the expression of mutant p53 protein and bcl-2 mRNA were decreased in all treatment groups (p<0.01), but there were no statistical difference between DDP control p and ASSF-DDP groups. The expression of caspase3 protein and bax mRNA was increased in all treatment groups, with statistical differences between the DDP and ASSF-DDP groups (p<0.01).
  
  
  CONCLUSIONS
  ASSF can inhibit bodyweight decrease caused by DDP, can inhibit tumor growth synergistically with DDP mainly through increasing serum HIF-1α and pro-apoptotic molecules such as caspase 3 and bax, rather than through decreasing anti-apoptotic mutant p53 and bcl-2. ASSF can reduce DDP toxicity due to decreasing the release of LDH, AST, ALT, AKP into blood and enhancing thymus protection.
authors: Gansu Traditional Chinese Medicine College, Lanzhou, China E-mail : yandq693@163.com, liuyongqi73@163.com.
authors: De-Qi
authors: DQ
authors: Yan
authors: Yong-Qi
authors: YQ
authors: Liu
authors: Ying-Dong
authors: YD
authors: Li
authors: Dou
authors: D
authors: Li
authors: Xiao-Li
authors: XL
authors: Cheng
authors: Zhi-Wei
authors: ZW
authors: Wu
mesh_terms: D029971:Angelica sinensis / Q000737:chemistry*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001835:Body Weight / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects* / Q000235:genetics; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D005663:Furans / Q000008:administration & dosage; D064593:Heterografts / Q000187:drug effects* / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D028321:Plant Preparations / Q000008:administration & dosage; D011753:Pyrones / Q000008:administration & dosage; D012333:RNA, Messenger / Q000235:genetics; D029909:Sophora / Q000737:chemistry*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C458502:2,6-dimethyldifuro-8-pyrone; D005663:Furans; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D028321:Plant Preparations; D011753:Pyrones; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D002945:Cisplatin