Inhibitors of mTOR overcome drug resistance from topoisomerase II inhibitors in solid tumors.

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.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Gaur S,Chen L,Yang L,Wu X,Un F,Yen Y

doi

10.1016/j.canlet.2011.06.005

subject

Has Abstract

pub_date

2011-12-01 00:00:00

pages

20-8

issue

1

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(11)00341-7

journal_volume

311

pub_type

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