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

研究成果: 雜誌貢獻文章同行評審

25 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
頁(從 - 到)20-28
頁數9
期刊Cancer Letters
311
發行號1
DOIs
出版狀態已發佈 - 12月 1 2011

ASJC Scopus subject areas

  • 腫瘤科
  • 癌症研究

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