mTOR inhibitor rapamycin alone or combined with cisplatin inhibits growth of esophageal squamous cell carcinoma in nude mice.
Accumulating evidences have demonstrated that mTOR pathway has a central role not only in cell growth but also in invasion and metastasis of cancers. Here we reported that rapamycin or cisplatin alone inhibited significantly the tumor growth and their combination had the strongest anticancer effect on transplantable tumor growth of human ESCC cell line EC9706 in nude mice. Furthermore, western blots, RT-PCR and TUNEL assay revealed that rapamycin specifically blocked mTOR pathway and induced apoptosis of ESCC cells in vivo. These findings indicate a rationale for using mTOR inhibitors as a mechanism-based therapeutic approach to patients with ESCC.
Zhengzhou University, Zhengzhou, China.
Guiqin
G
Hou
Qi
Q
Zhang
Lili
L
Wang
Mingyue
M
Liu
Jianren
J
Wang
Lexun
L
Xue
D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D047908:Intracellular Signaling Peptides and Proteins / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009374:Neoplasms, Experimental / Q000188:drug therapy; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D047908:Intracellular Signaling Peptides and Proteins; C546842:MTOR protein, human; C546843:mTOR protein, mouse; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D002945:Cisplatin; D020123:Sirolimus