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. 2011 Dec 1;311(1):20-8.
doi: 10.1016/j.canlet.2011.06.005. Epub 2011 Jun 29.

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

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

Shikha Gaur et al. Cancer Lett. .

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.

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