Norcantharidin enhances bortezomib-antimyeloma activity in multiple myeloma cells in vitro and in nude mouse xenografts

Abstract

Norcantharidin (NCTD), the demethylated analog of the Chinese medicine cantharidin, exhibits anti-myeloma activity by inactivating nuclear factor-κB (NF-κB), which is implicated in multiple myeloma (MM) cell survival and resistance to bortezomib (BTZ). We investigated whether NCTD could potentiate the anti-tumor activity of BTZ in MM. NCTD inhibited the proliferation of MM cells and potentiated the anti-myeloma effects of BTZ by down-regulating IKKα and p-IκBα, which induced the accumulation of IκBα and inhibited the constitutive activation of NF-κB. This effect was correlated with the suppression of NF-κB-regulated gene products. Furthermore, a chemotherapy-potentiating effect of NCTD on BTZ was also observed in vivo. Our study demonstrated that NCTD and BTZ exhibit significant therapeutic effects on MM through the NF-κB signal pathway in vitro and in vivo. Future studies will investigate the combined effects of NCTD and BTZ in patients with MM.

Keywords::

• Multiple myeloma
• bortezomib
• norcantharidin
• nuclear factor-κB
• cell survival
• apoptosis

Acknowledgement

We thank Medjaden Bioscience Limited for assisting in the preparation of this manuscript.

Potential conflict of interest: Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.