PMID- 25976336
OWN - NLM
STAT- MEDLINE
DCOM- 20161027
LR  - 20220317
IS  - 1973-9478 (Electronic)
IS  - 1120-009X (Linking)
VI  - 27
IP  - 6
DP  - 2015
TI  - Rapamycin enhanced the antitumor efficacy of oxaliplatin in cisplatin-resistant 
      ovarian cancer cells A2780cis both in vitro and in vivo.
PG  - 358-64
LID - 10.1179/1973947815Y.0000000021 [doi]
AB  - OBJECTIVE: This study aimed to investigate the efficacy of combination of 
      rapamycin, an mammalian target of rapamycin (mTOR) inhibitor for treating 
      rejection after organ transplantation, and oxaliplatin, a third-generation of 
      platinum drug usually used to treat chemoresistant or progressive ovarian cancer, 
      in cisplatin-resistant ovarian carcinoma cells A2780cis. METHODS/MATERIALS: 
      Expressions of mTOR and its target molecules p70S6K and 4E-BP1 were determined in 
      cisplatin-sensitive and -resistant cells A2780 and A2780cis, respectively, using 
      Western blotting. Proliferation of A2780cis exposure to oxaliplatin or 
      oxaliplatin plus rapamycin was examined using MTT assay in vitro as well as a 
      nude mice model in vivo. Cell apoptosis and proapoptosis proteins including 
      caspase-8 and -3 and PARP were determined using flow cytometry and Western 
      blotting. RESULTS: We found that A2780cis cells had partial cross-resistance 
      between cisplatin and oxaliplatin. The levels of phosphorylated mTOR (p-mTOR), 
      p70S6K, and 4E-BP1 were significantly increased in A2780cis cells compared to 
      A2780 cells, which might be implicated in cisplatin-induced chemoresistance. 
      Rapamycin obviously enhanced the inhibitory effect of oxaliplatin on the growth 
      of A2780cis both in vitro and in vivo. Rapamycin slightly induced cell apoptosis 
      but significantly enhanced the effect of oxaliplatin in soliciting apoptosis of 
      A2780cis cells, which might be ascribed to its ability in further increasing the 
      levels of cleaved caspase-8 and -3 and PARP induced by oxaliplatin. CONCLUSION: 
      These results suggested that combination of oxaliplatin and rapamycin enhanced 
      the antitumour efficacy of oxaliplatin in A2780cis cells and therefore might have 
      a role in treating cisplatin-resistant ovarian carcinoma.
FAU - Liu, Jin
AU  - Liu J
AD  - Department of Obstetrics and Gynecology, The Third People's Hospital of Liaocheng 
      , Shandong, China.
FAU - Zhang, Ling
AU  - Zhang L
FAU - Zhang, Xuehua
AU  - Zhang X
FAU - Xing, Xinli
AU  - Xing X
LA  - eng
PT  - Journal Article
DEP - 20150515
PL  - England
TA  - J Chemother
JT  - Journal of chemotherapy (Florence, Italy)
JID - 8907348
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (EIF4EBP1 protein, human)
RN  - 0 (Organoplatinum Compounds)
RN  - 0 (Phosphoproteins)
RN  - 04ZR38536J (Oxaliplatin)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 8)
RN  - Q20Q21Q62J (Cisplatin)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - Antineoplastic Combined Chemotherapy Protocols/*pharmacology
MH  - Apoptosis
MH  - Caspase 3/metabolism
MH  - Caspase 8/metabolism
MH  - Cell Cycle Proteins
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Cisplatin/*pharmacology
MH  - Drug Resistance, Neoplasm/*drug effects
MH  - Female
MH  - Humans
MH  - Mice
MH  - Mice, Nude
MH  - Organoplatinum Compounds/*pharmacology
MH  - Ovarian Neoplasms/*drug therapy
MH  - Oxaliplatin
MH  - Phosphoproteins/metabolism
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - Sirolimus/*pharmacology
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
MH  - Xenograft Model Antitumor Assays
OTO - NOTNLM
OT  - Cisplatin
OT  - Ovarian carcinoma
OT  - Oxaliplatin
OT  - Rapamycin
OT  - mTOR
EDAT- 2015/05/16 06:00
MHDA- 2016/11/01 06:00
CRDT- 2015/05/16 06:00
PHST- 2015/05/16 06:00 [entrez]
PHST- 2015/05/16 06:00 [pubmed]
PHST- 2016/11/01 06:00 [medline]
AID - 10.1179/1973947815Y.0000000021 [doi]
PST - ppublish
SO  - J Chemother. 2015;27(6):358-64. doi: 10.1179/1973947815Y.0000000021. Epub 2015 
      May 15.