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

doi:10.1016/j.canlet.2011.06.005

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 journal › Article › peer-review

25 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 language	English
Pages (from-to)	20-28
Number of pages	9
Journal	Cancer Letters
Volume	311
Issue number	1
DOIs	https://doi.org/10.1016/j.canlet.2011.06.005
Publication status	Published - Dec 1 2011

Keywords

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

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.canlet.2011.06.005

Cite this

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title = "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 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.",

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author = "Shikha Gaur and Linling Chen and Lixin Yang and Xiwei Wu and Frank Un and Yun Yen",

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T1 - Inhibitors of mTOR overcome drug resistance from topoisomerase II inhibitors in solid tumors

AU - Gaur, Shikha

AU - Chen, Linling

AU - Yang, Lixin

AU - Wu, Xiwei

AU - Un, Frank

AU - Yen, Yun

PY - 2011/12/1

Y1 - 2011/12/1

N2 - 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.

AB - 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.

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KW - Topoisomerase II

KW - γH2AX

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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