Effects of artesunate combined with bortezomib on apoptosis and autophagy of acute myeloid leukemia cells in vitro and its mechanism / 中华血液学杂志

Objective@#To investigate the effects of artesunate combined with bortezomib on the proliferation, apoptosis and autophagy of human acute myeloid leukemia cell lines MV4-11, and its mechanisms.@*Methods@#MTT method was used to determine the anti-proliferation effect of different concentrations of artesunate, bortezomib and their combination on MV4-11 cells. The cell apoptosis were analyzed by flow cytometry. The expression of cleaved-Caspase-3, Bcl-2 family protein (Bcl-2, Mcl-1, Bim, Bax) and autophagy-related protein LC3B were assayed by Western blot.@*Results@#Artesunate displayed a proliferation inhibition effect on MV4-11 with dose- and time-dependent manner, the IC50 of artesunate on MV4-11 after 48 hours was 1.44 μg/ml. Bortezomib displayed a proliferation inhibition effect on MV4-11 with dose-dependent manner, the IC50 of bortezomib on MV4-11 after 48 hours was 8.97 nmol/L. The combination of artesunate (0.75, 1.0 μg/ml) and Bortezomib (6, 8 nmol/L) showed higher inhibition on MV4-11 than artesunate or bortezomib alone in the same concentration gradient after 48 hours (P<0.05) . The cooperation index of the two drugs were all less than 1. The 48 h apoptotic rate of artesunate (1.5 μg/ml) on MV4-11 was (15.27±2.18) %, (19.85±3.23) % of bortezomib (8 nmol/L) , (81.67±5.96) % of combination of the two drugs, significantly higher than the single group (P<0.05) . When combination of the two drugs on MV4-11 after 24 hours, the levels of pro-apoptotic protein Bim and the cleaved activation of Caspase-3 and autophagy-related protein LC3B were up-regulated and the anti-apoptotic protein Bcl-2 expressions was down-regulated.@*Conclusion@#Combination of artesunate with bortezomib shows a significant synergistic effects on proliferation, apoptosis and autophagy of MV4-11 cell lines, which may be associated with Bcl-2 family proteins expression.

THE STUDY OF THE ARRANGEMENT OF FASCICLES OF MUSCULOCUTANEOUS NERVE IN THE BRACHIAL PLEXUS / 解剖学报

The arrangement of fascicles of musculocutaneous nerve at different levels in brachial plexus were studied in 22 adult cadavers. The nerve fascicles were dissociated and traced under operative microscope. At the distal end of the musculocutaneous nerve, the muscular and cutaneous fascicles are separated.The muscular fascicles are situated at the latero-anterior quadrant of the cross-section of the nerve.The mixed fascicle are become predominated proximally. The muscular and the muscular predominated mixed fascicles are still situated at latero-anterior quadrant. At the level 1 cm below the clevicle, 1cm and 1.5 cm above the clevicle,the fascicles of the nerve are situated at the lateral superio-anterior quadrant of the crosssection of relative parts of brachial plexus. The fascicles of the nerve are situated at the anterior quadrant of the crosssection of superior trunks. The fibers of musculocutaneous nerve are originate from C5, C6 and C7, being 31.6,％, 64.6％ and 3.8％,respectively.