title: Proteasome Inhibitor MG132 Enhances Sensitivity to Cisplatin on Ovarian Carcinoma Cells In Vitro and In Vivo.
abstract: Platinum-based combination chemotherapy after surgery is considered a standard treatment; therefore, any recent drug development should be new, effective, and low toxic, and should have a synergistic effect with platinum. This study aimed to observe the growth of SKOV3 cells after treatment with cisplatin by combining with carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (MG132) and to investigate the effect of the relationship between MG132 and cisplatin combination.
  
  
  
  Cell growth was detected by methyl thiazolyl tetrazolium assay after treatment with MG132 at 0.5, 1.5, 2.5, 3.5, and 5.0 μg/mL concentrations for 24, 48, and 72 hours; with cisplatin at 1.0, 2.0, 3.0, 4.0, and 5.0 μg/mL concentrations; and with combination with MG132 at 1.5 μg/mL for 24 hours. The apoptotic rates of cells were detected by a flow cytometer after cisplatin treatment at 1.0, 2.0, 3.0, and 4.0 μg/mL concentrations and that combined with MG132 at 1.5 μg/mL concentration for 12, 24, and 36 hours. A total of 20 BALB/c (nu/nu) female nude mice (age, 4-6 weeks; body weight, 17-19 g) were divided into 4 groups: control, MG132, cisplatin, and combination groups. The expression of Caspase3 and Beclin1 was detected by Western blot analysis and reverse transcription-polymerase chain reaction after treatment with 3.0 μg/mL of the cisplatin group and combined treatment with 1.5 μg/mL of MG132 group for 24 hours, respectively.
  
  
  
  Methyl thiazolyl tetrazolium assay demonstrated the inhibitory rates, and the flow cytometery showed that the apoptotic rates in the combination group were higher than those in the cisplatin group (P < 0.01). Western blot analysis and reverse transcription-polymerase chain reaction detected that Caspase3 and Beclin1 at a relative quantity in the combination group were higher than those in the cisplatin group (P < 0.05).
  
  
  
  MG132 has a synergistic antitumor effect by combining with cisplatin, and it is expected to be an effective antitumor drug for platinum-resistant refractory ovarian cancer.
authors.affiliation: Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China.
authors.forename: Na
authors.initials: N
authors.lastname: Guo
authors.forename: Zhilan
authors.initials: Z
authors.lastname: Peng
authors.forename: Jiawen
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D000077216:Carcinoma, Ovarian Epithelial; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D015853:Cysteine Proteinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007976:Leupeptins / Q000008:administration & dosage / Q000494:pharmacology*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D011897:Random Allocation; D023041:Xenograft Model Antitumor Assays
chemical_list: D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D002945:Cisplatin; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde