کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2116361 | 1084854 | 2011 | 9 صفحه PDF | دانلود رایگان |
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.
► Combination of mTOR inhibitors with Topoisomerase II inhibitors.
► Combination is synergistic in head and neck and breast cancer cells.
► mTOR inhibitor sensitizes adriamycin/cisplatin resistant cells.
► DNA repair is required after induction of DNA damage by topoisomerase II inhibitors.
► mTOR inhibitor restores chemosensitivity by blocking the translation of proteins.
Journal: Cancer Letters - Volume 311, Issue 1, 1 December 2011, Pages 20–28