Abstract |
The present study was performed to investigate the possible role of mTOR inhibitors in restoring chemosensitivity to adriamycin/ cisplatin and elucidate the underlying mechanism. Combining adriamycin/ cisplatin with torisel synergistically inhibited the cell proliferation in human oropharyngeal carcinoma cell line KB and its multidrug-resistant subclone KB/7D. Combining adriamycin and torisel inhibited the phosphorylation of 4EBP-1 and p70S6K, the proteins involved in mTOR pathway, increased expression of γH2AX indicative of DNA damage, triggered cell cycle arrest at G2/M and apoptosis. We conclude that chromatin decondensation by DNA damage provided an easy access for torisel to block the translation of proteins essential for DNA repair thereby restoring the chemosensitivity.
|
Authors | Shikha Gaur, Linling Chen, Lixin Yang, Xiwei Wu, Frank Un, Yun Yen |
Journal | Cancer letters
(Cancer Lett)
Vol. 311
Issue 1
Pg. 20-8
(Dec 01 2011)
ISSN: 1872-7980 [Electronic] Ireland |
PMID | 21764510
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright © 2011 Elsevier Ireland Ltd. All rights reserved. |
Chemical References |
- Eukaryotic Initiation Factors
- Topoisomerase II Inhibitors
- temsirolimus
- Doxorubicin
- Everolimus
- MTOR protein, human
- Ribosomal Protein S6 Kinases, 70-kDa
- TOR Serine-Threonine Kinases
- DNA Topoisomerases, Type II
- Cisplatin
- Sirolimus
|
Topics |
- Antineoplastic Combined Chemotherapy Protocols
(pharmacology)
- Apoptosis
(drug effects)
- Breast Neoplasms
(drug therapy, enzymology, genetics, pathology)
- Cell Cycle
(drug effects)
- Cell Line, Tumor
- Cisplatin
(administration & dosage)
- DNA Damage
- DNA Repair
- DNA Topoisomerases, Type II
(metabolism)
- Doxorubicin
(administration & dosage)
- Drug Resistance, Neoplasm
- Drug Synergism
- Eukaryotic Initiation Factors
(metabolism)
- Everolimus
- Female
- Head and Neck Neoplasms
(drug therapy, enzymology, genetics, pathology)
- Humans
- Phosphorylation
(drug effects)
- Ribosomal Protein S6 Kinases, 70-kDa
(metabolism)
- Sirolimus
(administration & dosage, analogs & derivatives)
- TOR Serine-Threonine Kinases
(antagonists & inhibitors, metabolism)
- Topoisomerase II Inhibitors
(administration & dosage, pharmacology)
|