Combination of Inhibitors of USP7 and PLK1 has a Strong Synergism against Paclitaxel Resistance
Department of Pharmacy, College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi-do 15588, Korea
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Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(22), 8629; https://doi.org/10.3390/ijms21228629
Received: 30 October 2020
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Revised: 10 November 2020
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Accepted: 12 November 2020
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Published: 16 November 2020
(This article belongs to the Special Issue Molecular Target and Action Mechanism of Anti-Cancer Agents)
USP7 is a promising target for the development of cancer treatments because of its high expression and the critical functions of its substrates in carcinogenesis of several different carcinomas. Here, we demonstrated the effectiveness of targeting USP7 in advanced malignant cells showing high levels of USP7, especially in taxane-resistant cancer. USP7 knockdown effectively induced cell death in several cancer cells of lung, prostate, and cervix. Depletion of USP7 induced multiple spindle pole formation in mitosis, and, consequently, resulted in mitotic catastrophe. When USP7 was blocked in the paclitaxel-resistant lung cancer NCI-H460TXR cells, which has resistance to mitotic catastrophe, NCI-H460TXR cells underwent apoptosis effectively. Furthermore, combination treatment with the mitotic kinase PLK1 inhibitor volasertib and the USP7 inhibitor P22077 showed a strong synergism through down-regulation of MDR1/ABCB1 in paclitaxel-resistant lung cancer. Therefore, we suggest USP7 is a promising target for cancer therapy, and combination therapy with inhibitors of PLK1 and USP7 may be valuable for treating paclitaxel-resistant cancers, because of their strong synergism.
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Keywords:
USP7; PLK1; taxane; chemoresistance; combination
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MDPI and ACS Style
Shin, S.-B.; Kim, C.-H.; Jang, H.-R.; Yim, H. Combination of Inhibitors of USP7 and PLK1 has a Strong Synergism against Paclitaxel Resistance. Int. J. Mol. Sci. 2020, 21, 8629. https://doi.org/10.3390/ijms21228629
AMA Style
Shin S-B, Kim C-H, Jang H-R, Yim H. Combination of Inhibitors of USP7 and PLK1 has a Strong Synergism against Paclitaxel Resistance. International Journal of Molecular Sciences. 2020; 21(22):8629. https://doi.org/10.3390/ijms21228629
Chicago/Turabian StyleShin, Sol-Bi, Chang-Hyeon Kim, Hay-Ran Jang, and Hyungshin Yim. 2020. "Combination of Inhibitors of USP7 and PLK1 has a Strong Synergism against Paclitaxel Resistance" International Journal of Molecular Sciences 21, no. 22: 8629. https://doi.org/10.3390/ijms21228629
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