title: Targeting renal cell carcinoma with gambogic acid in combination with sunitinib in vitro and in vivo.
abstract: OBJECTIVE
  To evaluated the effect of the gambogic acid (GA), one of the effective components of Garcinia, in combination with a new multi-targeted oral medication, sunitinib (SU) on renal cancer cell proliferation in vitro and on tumor growth in vivo.
  
  
  METHODS
  After treatment with GA or SU, either alone or in combination, MTT and FACS analysis were used to examine cell viability and cycle distribution of the renal carcinoma cell lines 786-0 and Caki-1. Western blotting was employed to examine the expression of proteins related to the cell cycle and vascular formation. Furthermore, a xenograft model was applied to study the antitumor efficacy of SU or GA alone or in combination, with immunohistochemistry to detect expression of proteins related to xenograft growth and angiogenesis. Western blotting was used to examine NF-?B signaling pathway elements in xenografts.
  
  
  RESULTS
  Treatment of 786-0 and Caki-1 cells with GA or SU resulted in decreased tumor cell proliferation, especially with joint use. Cells accumulated more strongly in the sub-G1 phase after joint treatment with GA and SU than treatment of GA and SU alone. Western blotting arrays showed 1 protein significantly upregulated, 2 proteins downregulated, and 2 proteins unchanged. Moreover, combined use of GA and SU inhibited the growth and angiogenesis of xenografts generated from Caki-1 significantly. Immunohistochemistry arrays showed downregulation of the expression of proteins promoting xenograft growth and angiogenesis, and Western blotting showed inhibition of the NF-?B signaling pathway after treatment by GA alone and in combination with SU in xenografts.
  
  
  CONCLUSIONS
  Our results show that the joint use of GA and SU can provide greater antitumor efficacy compared to either drug alone and thus may offer a new treatment strategy for renal cell carcinoma.
authors: Department of Urology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China. 14246385@qq.com
authors: Xiao-Liang
authors: XL
authors: Jiang
authors: Yao
authors: Y
authors: Zhang
authors: Chun-Li
authors: CL
authors: Luo
authors: Xiao-Hou
authors: XH
authors: Wu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D016193:G1 Phase / Q000187:drug effects / Q000235:genetics; D007211:Indoles / Q000008:administration & dosage; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016328:NF-kappa B / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000235:genetics; D011758:Pyrroles / Q000008:administration & dosage; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D000077210:Sunitinib; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D044004:Xanthones / Q000008:administration & dosage; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D016328:NF-kappa B; D011758:Pyrroles; D044004:Xanthones; C052659:gambogic acid; D000077210:Sunitinib