Figure 1

Aloperine inhibits the growth of human MM cell lines and primary MM cells but not BMSCs or PBMCs. (A, B) MM cell lines were treated with the indicated doses of aloperine or vehicle for 48 h (A) or 80 μM aloperine for 72 h (B). Proliferation was measured using MTS assays, and IC50 values for different cell lines ranged from 80 to 260 μM. (C) MTS assays were performed on purified MM cells from 12 patients with relapsed MM whose diseases were resistant to chemotherapy, normal PBMCs, and malignant MM-derived BMSCs; two representative cases are shown. In all experiments, cells were treated for 48 h with graded doses of aloperine (^a,b P < 0.001 versus all patient MM cells). (D) Aloperine inhibited the proliferation of MM cells adhering to BMSCs. After BMSCs reached confluence in a 96-well plate, U266 and MM.1S cells were added and allowed to adhere for 4 h. Aloperine was added at the indicated doses, and BrdUrd proliferation assays were performed after 48 h of co-culture. BMSCs alone and MM cell lines alone served as controls (^a P < 0.001 versus U266 and MM.1S cells). (E) Aloperine overcomes the protective effects of recombinant human IL-6 and recombinant human IGF-I. MM.1S and U266 cells were treated for 48 h with the indicated concentrations of aloperine in the presence or absence of rhIL-6 and rhIGF-I at the indicated doses, and MTS assays were used to measure proliferation (^a P < 0.05 versus U266 and MM.1S, respectively). Data represent the means ± SD (n = 3). The results illustrate a representative experiment (n = 3).