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

Shikha Gaur, Linling Chen, Lixin Yang, Xiwei Wu, Frank Un, Yun Yen

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)20-28
Number of pages9
JournalCancer Letters
Volume311
Issue number1
DOIs
Publication statusPublished - Dec 1 2011
Externally publishedYes

Fingerprint

Topoisomerase II Inhibitors
Drug Resistance
Doxorubicin
Cisplatin
DNA Damage
G2 Phase Cell Cycle Checkpoints
Neoplasms
Protein Biosynthesis
DNA Repair
Chromatin
Phosphorylation
Cell Proliferation
Apoptosis
Carcinoma
Cell Line
temsirolimus

Keywords

  • γH2AX
  • Chemotherapeutic drugs
  • DNA damage
  • G2/M arrest
  • MTOR
  • Topoisomerase II

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Inhibitors of mTOR overcome drug resistance from topoisomerase II inhibitors in solid tumors. / Gaur, Shikha; Chen, Linling; Yang, Lixin; Wu, Xiwei; Un, Frank; Yen, Yun.

In: Cancer Letters, Vol. 311, No. 1, 01.12.2011, p. 20-28.

Research output: Contribution to journalArticle

Gaur, Shikha ; Chen, Linling ; Yang, Lixin ; Wu, Xiwei ; Un, Frank ; Yen, Yun. / Inhibitors of mTOR overcome drug resistance from topoisomerase II inhibitors in solid tumors. In: Cancer Letters. 2011 ; Vol. 311, No. 1. pp. 20-28.
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