title: [ASPP2 inhibits oxaliplatin-induced autophagy and promotes apoptosis of colon cancer cells].
abstract: OBJECTIVE
  To investigate the role of apoptosis stimulating p53 binding protein 2 (ASPP2)-induced p53-dependent and p53-independent autophagy inhibition in apoptosis-promoting function of oxaliplatin (OXA).
  
  
  METHODS
  According to different treatments, HCT116(p53(-/-)) cells were divided into 6 groups: rapamycin combined with ASPP2 group, ASPP2 group, p53 group, ASPP2 combined with p53 group, OXA combined with 3-methyladenine (3-MA) group, control group (OXA treatment or starvation without OXA treatment). When the level of apoptosis was detected, green fluorescent protein-advirus (GFP-Ad) group and rapamycin group were supplemented as controls. Cells were transfected with GFP-microtubule-associated protein 1 light chain 3 (GFP-LC3) plasmid, and LC3-expressing cells were calculated under a fluorescent microscope. Expressions of autophagy-related molecules were detected by Western blotting. Cells were subjected to annexin V-FITC/PI staining and apoptosis was assessed by flow cytometry.
  
  
  RESULTS
  The 3-MA group showed the same inhibitory ability on autophagy with the ASPP2 group, and both of them were able to promote OXA or starvation-induced apoptosis, but the cell apoptosis rate in the 3-MA group was lower than that of the ASPP2 group. Rapamycin combined with ASPP2 still promoted OXA or starvation-induced apoptosis, and the apoptosis rate was also lower than that of the ASPP2 group. However, rapamycin counteracted effectively the inhibitory effect of ASPP2 on autophagy.
  
  
  CONCLUSIONS
  OXA can induce autophagy of colorectal cancer cells, while ASPP2 over-expression can suppress the OXA-induced autophagy. ASPP2 can promote apoptosis through p53-dependent and p53-independent pathways. The function of ASPP2 promoting cell apoptosis through p53-dependent and p53-independent pathways is not entirely achieved by inhibiting cell autophagy.
authors.affiliation: Department of General Surgery, Tumor Hospital of Shandong Province, Jinan 250117; School of Medicine and Life Science, Shandong Academy of Medical Sciences, University of Jinan, Jinan 250022, China.
authors.forename: Bishi
authors.initials: B
authors.lastname: Wang
authors.affiliation: Beijing Institute of Liver Disease, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China.
authors.forename: Luxin
authors.initials: L
authors.lastname: Qiao
authors.affiliation: Beijing Institute of Liver Disease, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of General Surgery, Tumor Hospital of Shandong Province, Jinan 250117; School of Medicine and Life Science, Shandong Academy of Medical Sciences, University of Jinan, Jinan 250022, China.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Feng
authors.affiliation: Beijing Institute of Liver Disease, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China.
authors.forename: Dexi
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Tumor Hospital of Shandong Province, Jinan 250117, China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Guo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001343:Autophagy / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000473:pathology*; D045325:HCT116 Cells; D006801:Humans; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D009944:Organoplatinum Compounds; C090468:TP53BP2 protein, human; D016159:Tumor Suppressor Protein p53; D000077150:Oxaliplatin