title: Chloroquine promotes the anticancer effect of TACE in a rabbit VX2 liver tumor model.
abstract: BACKGROUND
  To investigate the efficacy of TACE combined with CQ, an autophagic inhibitor, in a rabbit VX2 liver tumor model.
  
  
  METHODS
  Tumor size was measured. And tumor growth rate was calculated to examine the effect of the combined treatment. Apoptosis was detected by TUNEL assay. Meanwhile, autophagic activity was detected by immunohistochemistry and Western blotting to investigate the mechanism underlying. Liver function was also examined to assess feasibility and safety of the combined therapy.
  
  
  RESULTS
  Tumors in the control grew more than 4 times bigger after 14 days, while that in the group of TACE alone just showed mild growth. But a slight shrinkage was shown after the treatment of CQ+TACE. Growth ratio of TACE alone was 96.45% ± 28.958% while that of CQ+TACE was -28.73% ± 12.265%. Compared with TACE alone, necrosis in CQ+TACE showed no significant difference, however, the apoptosis was much higher. There were only 14.8±3.11% apoptotic cells in TACE, but 33±4.18% in CQ+TACE, which suggests the increased apoptosis in CQ+TACE contributed to the decrease of tumor volume. In terms of autophagic activity, the result is negative when we immunostained sections of the control with LC3 antibody, but positive in TACE alone and CQ+TACE. And the result of Western blot showed that there was just a low level of LC3Ⅱexpressed in the control and CQ alone, but higher in TACE, and much higher in CQ+TACE because CQ inhibited its degradation in autophagy. Compared with control, p62 decreased in TACE, but the decrease was partially reversed in CQ+TACE. In addition, toxicity of CQ+TACE was assessed not higher than TACE alone, which supports the safety of CQ+TACE.
  
  
  CONCLUSIONS
  CQ+TACE works better than TACE alone in rabbit VX2 liver tumor model because CQ inhibits autophagy induced by TACE. The inhibited autophagy loses its resistance to apoptosis that apoptosis increased, which contributes to the inhibition of tumor growth. This study indicates CQ may be a promising adjuvant to promote the effect of TACE.
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200438, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Gao
authors.forename: Jian-rui
authors.initials: JR
authors.lastname: Song
authors.forename: Jian-wei
authors.initials: JW
authors.lastname: Zhang
authors.forename: Xue
authors.initials: X
authors.lastname: Zhao
authors.forename: Qiu-dong
authors.initials: QD
authors.lastname: Zhao
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.forename: Wei-jie
authors.initials: WJ
authors.lastname: Deng
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.forename: Gang
authors.initials: G
authors.lastname: Lv
authors.forename: Hong-yan
authors.initials: HY
authors.lastname: Cheng
authors.forename: Li-xin
authors.initials: LX
authors.lastname: Wei
mesh_terms: D051722:ADAM Proteins / Q000627:therapeutic use*; D000072198:ADAM17 Protein; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002738:Chloroquine / Q000627:therapeutic use*; D004357:Drug Synergism; D020287:In Situ Nick-End Labeling; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011817:Rabbits
chemical_list: D000970:Antineoplastic Agents; D002738:Chloroquine; D051722:ADAM Proteins; D000072198:ADAM17 Protein
keywords: Hepatocellular carcinoma; apoptosis; autophagy.; chloroquine; transcatheter arterial chemoembolization