Objective: To investigate the effects of Artesunate on suppressing the proliferation of Bortezomib-resistant multiple myeloma (MM) cell line and to explore its molecular mechanism on reversal of drug resistance. Method: Human MM cell line NCI-H929 was treated with Bortezomib in a dose-dependent manner to establish Bortezomib-resistant cell line NCI-H929BR. The inhibitory role of Artesunate on NCI-H929BR and its reversal effect against Bortezomib-resistance were determined by methylthiazolyldiphenyl-tetrazolium bromide(MTT) assay. Cell apoptosis was determined by flow cytometry

and the protein expression levels of nuclear factor-κB p65 (NF-κB p65)

phospho-nuclear factor-κB p65 (NF-κB p-p65)

P-glycoprotein (P-gp)

B-cell lymphoma/leukemia-2 (Bcl-2) protein and Bcl-2 associated X protein (Bax) were detected by Western blot assay. Result: Bortezomib-resistance index of NCI-H929BR was 20.2 times. Artesunate treatment had significant inhibitory effect on the proliferation of NCI-H929BR and the inhibitory effect was in a concentration-dependent manner. Bortezomib (50 nmol·L-1)alone had less effect on NCI-H929BR proliferation

while the inhibition rate of artesunate (12.5 mg·L-1) alone was (23.53±2.21)% (P<0.05); Bortezomib combined with artesunate treatment had greater inhibitory effect (60.71±3.43)% (P<0.01). Artesunate treatment increased NCI-H929BR apoptosis

down-regulated NF-κB p65

NF-κB p-p65

P-gp and Bcl-2 expression levels

and up-regulated Bax expression level in a concentration-dependent manner. Conclusion: Artesunate could inhibit NCI-H929BR proliferation

promote apoptosis and reverse Bortezomib-resistance

and its mechanism may be associated with down-regulating expression levels of NF-κB p65

NF-κB p-p65

P-gp

Bcl-2 and up-regulating expression level of Bax.