Title of article
Inhibitors of mTOR overcome drug resistance from topoisomerase II inhibitors in solid tumors
Author/Authors
Gaur، نويسنده , , Shikha and Chen، نويسنده , , Linling and Yang، نويسنده , , Lixin and Wu، نويسنده , , Xiwei and Un، نويسنده , , Frank and Yen، نويسنده , , Yun، نويسنده ,
Issue Information
روزنامه با شماره پیاپی سال 2011
Pages
9
From page
20
To page
28
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 p70S6 K, 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.
Keywords
?H2AX , DNA damage , mTOR , Chemotherapeutic drugs , G2/M arrest , Topoisomerase II
Journal title
Cancer Letters
Serial Year
2011
Journal title
Cancer Letters
Record number
1820428
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