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15 January 2018 : Animal Research  

Proteasome Inhibitor Carbobenzoxy-L-Leucyl-L-Leucyl-L-Leucinal (MG132) Enhances Therapeutic Effect of Paclitaxel on Breast Cancer by Inhibiting Nuclear Factor (NF)-κB Signaling

Yunjing Zhang1ABCDEF, Bin Yang1BCF, Jinping Zhao1BCF, Xiaoli Li1BC, Long Zhang1BD, Zhenhua Zhai12ACEFG*

DOI: 10.12659/MSM.908139

Med Sci Monit 2018; 24: ANS294-304

Abstract

BACKGROUND: Carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (MG132), a peptide aldehyde proteasome inhibitor, can inhibit tumor progression by inactivating nuclear factor (NF)-κB signaling. Paclitaxel (PTX) is part of a routine regimen for the treatment of breast cancer. However, activation of the NF-κB pathway after treatment with PTX confers insensitivity to this drug. This study investigated the potential effect of MG132 as a co-treatment with PTX against breast cancer, and clarifies the underlying molecular mechanisms.

MATERIAL AND METHODS: Breast cancer cells were treated with PTX, MG132, or PTX plus MG132, and the therapeutic effects were evaluated phenotypically. A mouse model of breast cancer was used to determine the combined effect of PTX plus MG132 in vivo.

RESULTS: Treatment with PTX plus MG132 suppressed aggressive phenotypes of breast cancer cells more effectively than PTX alone. Consistently, MG132 also enhanced the suppressive effect of PTX on tumor growth in C57BL/6 mice. Significantly, activation of the NF-κB pathway by PTX was attenuated by MG132.

CONCLUSIONS: Based on our findings, we suggest the application of MG132 in clinical practice in combination with PTX for the treatment of breast cancer.

Keywords: NF-kappa B, paclitaxel, Proteasome Inhibitors

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Medical Science Monitor Basic Research eISSN: 2325-4416
Medical Science Monitor Basic Research eISSN: 2325-4416