title: Combination of temsirolimus and adriamycin exhibits an enhanced antitumor effect in hepatocellular carcinoma.
abstract: OBJECTIVE
  The oncogenic PI3K/Akt/mTOR pathway is frequently activated in hepatocellular carcinoma (HCC). The aim of this study is to investigate the anti-HCC effect of combination of temsirolimus, an mTOR inhibitor, and adriamycin, a routinely used drug for treating HCC.
  
  
  METHODS
  Proliferation of HCC cells exposure to temsirolimus, adriamycin, and their combination was determined using MTT assay in vitro as well as in a nude mice model in vivo. Cell apoptosis was examined using flow cytometry. Expressions of apoptosis-related proteins including caspase-9, -3, PARP, Bax, and Bcl-2 were determined using Western blotting.
  
  
  RESULTS
  Temsirolimus plus adriamycin showed an enhanced inhibitory effect on cell proliferation compared to temsirolimus or adriamycin in HCC cells PLC/PRF/5, BEL7402, and HuH7 in vitro. The drug combination solicited a higher percentage of apoptosis cells and induced higher levels of cleaved caspase-9, -3, and PARP than temsirolimus or adriamycin used alone. The ratio of Bax/Bcl-2 was increased in cells exposed to the combination treatment. The enhanced anti-tumor effect of this drug combination was verified in a nude mice model. We also observed that half doses of temsirolimus and adriamycin used in combination achieved a comparable tumor growth inhibitor rate with full dose of temsirolimus or adriamycin used alone.
  
  
  CONCLUSIONS
  Temsirolimus plus adriamycin exhibited an enhanced antitumor effect in HCC and this drug combination might have a potential value in treatment of HCC. Studies are warranted to comprehensively evaluate the efficacy and safety of this regimen in the future.
authors.affiliation: Department of Oncology, Liaocheng People's Hospital, Liaocheng, China.
authors.forename: Hong-Gang
authors.initials: HG
authors.lastname: Kang
authors.affiliation: Department of Oncology, Liaocheng People's Hospital, Liaocheng, China.
authors.forename: Bao-Zhong
authors.initials: BZ
authors.lastname: Wang
authors.affiliation: Department of Oncology, Liaocheng People's Hospital, Liaocheng, China. Electronic address: zhangjingsd@outlook.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Liaocheng People's Hospital, Liaocheng, China.
authors.forename: Mei-Rong
authors.initials: MR
authors.lastname: Liu
authors.affiliation: Department of Pathology, Liaocheng People's Hospital, Liaocheng, China.
authors.forename: Ying-Xue
authors.initials: YX
authors.lastname: Li
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D053148:Caspase 3 / Q000032:analysis; D053453:Caspase 9 / Q000032:analysis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D011065:Poly(ADP-ribose) Polymerases / Q000032:analysis; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; C401859:temsirolimus; D004317:Doxorubicin; D011065:Poly(ADP-ribose) Polymerases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D053148:Caspase 3; D053453:Caspase 9; D020123:Sirolimus