Mechanism of Triptolide Liposome Nanoparticles on Apoptosis of Multiple Myeloma Cells Induced by Bortezomib

Abstract

The aim of this research was to investigated the effects of triptolide (TP) and its liposome nanoparticles (TP-LNP) on the apoptosis of multiple myeloma (MM) cells induced by Bortezomi. The encapsulation rate (ER), drug loading (DL), particle size (PS), and Zeta potential characteristics of the TP-LNP were evaluated. MMT assay was employed to detect the inhibitory effect of TP single agent and TP-LNP on proliferation of MM cells. MM cells were enrolled into a control group (Ctrl group, no intervention), a Bortezomi group (75 nM Bortezomi intervention 12 h), a Bortezomi +TP group (Bortezomi combined with TP monotherapy), and a Bortezomi+TP-LNP group (Bortezomi combined with TP-LNP). CCK-8, flow cytometry, and Western blot were utilized to detect the cell survival rate (SR), apoptosis, and MAPK/ERK pathway related protein, respectively. The results revealed that the shape of TP-LNP was similar to circular and uniformly distributed. Its average PS was (181.2±6.3) nm, the average Zeta potential was −29.15 mV, the average ER was 82.1%, and the average DL was 1.09%. When the drug concentration was 100 nmol/L, the inhibition rates of cell proliferation of TP and TP-LNP were (66.8±0.5)% and (81.4±0.6)%, respectively; and their median inhibitory concentrations (MICs) after 72 h were (89.5±1.8) nmol/L and (55.3±2.2) nmol/L, respectively. Based on the Ctrl group, the SRs in the Bortezomi, Bortezomi+TP, and Bortezomi+TP-LNP groups were decreased obviously, while the apoptosis rates were increased, and the comparisons herein exhibited great differences with P <0.05. The SR in the Bortezomi+TP-LNP group was the lowest and the apoptosis rate was the highest, showing great differences among the three groups (P < 0.05). Based on the Ctrl group, the expressions of P-P38 and P-ErK in the Bortezomi, Bortezomi+TP, and Bortezomi+TP-LNP groups were decreased (P <0.05). The levels of P-P38 and P-Erk in the Bortezomi+TP-LNP group were the lowest, and the differences in those in this group and the Bortezomi and the Bortezomi+TP groups statistically great (P <0.05). TP-LNP could inhibit the activation of MAPK/ERK pathway, enhance the apoptosis of MM cells induced by Bortezomi, and inhibit the cell proliferation.