Overexpression of survivin via activation of ERK1/2, Akt, and NF-κB plays a central role in vincristine resistance in multiple myeloma cells

Leukemia Research
Masanobu TsubakiShozo Nishida

Abstract

The acquisition of anti-cancer drug resistance is a major limitation of chemotherapy for multiple myeloma (MM) and it is thus important to identify the mechanisms by which MM cells develop such drug resistance. In a previous study, we showed that multidrug resistance (MDR) involves the overexpression of MDR1 and survivin in vincristine-resistant RPMI8226/VCR cells. However, the underlying mechanism of MDR remains unclear. In this study, we investigated the mechanism of MDR in RPMI8226/VCR cells, and found that RPMI8226/VCR cells exhibit increased levels of activated ERK1/2, Akt, and NF-κB, while the levels of activated mTOR, p38MAPK, and JNK do not differ between RPMI8226/VCR cells and their vincristine-susceptible counterparts. In addition, the inhibition of ERK1/2, Akt, or NF-κB by inhibitors reversed the drug-resistance of RPMI8226/VCR cells via the suppression of survivin expression, but did not affect MDR1 expression; RNA silencing of survivin expression completely reversed vincristine resistance, while MDR1 silencing only weakly suppressed vincristine resistance in RPMI8226/VCR cells. These results indicate that enhanced survivin expression via the activation of ERK1/2, Akt, and NF-κB plays a critical role in vincristine ...Continue Reading

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Citations

Jan 15, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Masanobu TsubakiShozo Nishida
Jan 10, 2016·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Zakir KhanPrakash Singh Bisen
Jun 30, 2015·Cancer Letters·Changqing Su
Nov 9, 2016·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Xin ChenJin-Jian Lu
Oct 21, 2016·Autophagy·Ya-Qin TanGang Zhou
Apr 20, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Lei ZhangYang Wang
Oct 27, 2017·Apoptosis : an International Journal on Programmed Cell Death·Mervat S MohamedAyat G Ali
Jun 6, 2018·Current Osteoporosis Reports·Jonathan D DiedrichIzabela Podgorski
Mar 9, 2020·Cancer Chemotherapy and Pharmacology·Parthasaradhireddy TanguturiSuresh Ramakrishna
Jul 12, 2017·Oncology Letters·Zhongjie Xu, Lirong Zhang
Oct 24, 2017·Journal of Cellular Physiology·Masanobu TsubakiShozo Nishida
Apr 24, 2019·International Journal of Molecular Sciences·Marta Ewelina WawroJolanta Niewiarowska
Jul 26, 2016·Experimental and Therapeutic Medicine·Hua YangYuren Xi
Feb 6, 2017·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Shozo Nishida, Masanobu Tsubaki
Mar 17, 2020·BMC Complementary Medicine and Therapies·Mitsuki TabataShozo Nishida
Sep 1, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Zi-Gang ZhenLu Jia
Feb 19, 2021·Cellular and Molecular Life Sciences : CMLS·Sinan XiongJianbiao Zhou

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