title: Residual hepatocellular carcinoma after oxaliplatin treatment has increased metastatic potential in a nude mouse model and is attenuated by Songyou Yin.
abstract: BACKGROUND
  The opposite effects of chemotherapy, which enhance the malignancy of treated cancers such as hepatocellular carcinoma (HCC), are not well understood. We investigated this phenomenon and corresponding mechanisms to develop a novel approach for improving chemotherapy efficacy in HCC.
  
  
  METHODS
  Human hepatocellular carcinoma cell lines HepG2 (with low metastatic potential) and MHCC97L (with moderate metastatic potential) were used for the in vitro study. An orthotopic nude mouse model of human HCC was developed using MHCC97L cells. We then assessed the metastatic potential of surviving tumor cells after in vitro and in vivo oxaliplatin treatment. The molecular changes in surviving tumor cells were evaluated by western blot, immunofluorescence, and immunohistochemistry. The Chinese herbal extract Songyou Yin (composed of five herbs) was investigated in vivo to explore its effect on the metastatic potential of oxaliplatin-treated cancer cells.
  
  
  RESULTS
  MHCC97L and HepG2 cells surviving oxaliplatin treatment showed enhanced migration and invasion in vitro. Residual HCC after in vivo oxaliplatin treatment demonstrated significantly increased metastasis to the lung (10/12 vs. 3/12) when re-inoculated into the livers of new recipient nude mice. Molecular changes consistent with epithelial-mesenchymal transition (EMT) were observed in oxaliplatin-treated tumor tissues and verified by in vitro experiments. The Chinese herbal extract Songyou Yin (4.2 and 8.4 g/kg) attenuated EMT and inhibited the enhanced metastatic potential of residual HCC in nude mice (6/15 vs. 13/15 and 3/15 vs. 13/15, respectively).
  
  
  CONCLUSIONS
  The surviving HCC after oxaliplatin treatment underwent EMT and demonstrated increased metastatic potential. Attenuation of EMT by Songyou Yin may improve the efficacy of chemotherapy in HCC.
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
authors.forename: Zheng-Gang
authors.initials: ZG
authors.lastname: Ren
authors.forename: Shuang-Jian
authors.initials: SJ
authors.lastname: Qiu
authors.forename: Hui-Chuan
authors.initials: HC
authors.lastname: Sun
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Bin-Bin
authors.initials: BB
authors.lastname: Liu
authors.forename: Qi-Song
authors.initials: QS
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Zhu
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
authors.forename: Wen-Quan
authors.initials: WQ
authors.lastname: Wang
authors.forename: Zhao-You
authors.initials: ZY
authors.lastname: Tang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000556:secondary; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D054338:Cell Transdifferentiation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D056945:Hep G2 Cells; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D018365:Neoplasm, Residual / Q000188:drug therapy* / Q000556:secondary; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D013997:Time Factors; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D009944:Organoplatinum Compounds; C551424:songyou yin; D000077150:Oxaliplatin