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Fig. 2 | Journal of Hematology & Oncology

Fig. 2

From: A novel role of lysophosphatidic acid (LPA) in human myeloma resistance to proteasome inhibitors

Fig. 2

LPAR2 deficiency or inhibition sensitizes human MM cells to PI treatment through regulating mitochondrial OXPHOS-mediated ER protein folding/refolding and proteasome activity. a Heatmap showing the relative expression of LPAR2 and genes involved in protein folding/refolding in ER in normal plasma cells and patient-derived MM cells from GSE15695. b Correlations between LPAR2 and gene cluster involved in protein fold/refolding in ER, including PPIB, CANX, GANAB, HSPBP1, PIAD4, PFDN1, CALR, CCT5, CCT6A, ERP44, DNAJA1, DNAJB11, HSPA5, and PPIA, in patient-derived MM cells from GSE15695. c–e Bar graphs depicting the summarized results of the reduced/oxidized meroGFP in ER (c), the ATP/ADP ratio in ER (d) and cytosol (e) of ARP1, MM.1S, and MM.1R cells treated without (PBS) or with 4 μg/mL LPA. f ARP1 and MM.1S cells were pre-treated with vehicle (PBS), LPA (4 μg/mL), vehicle + PD184352 (5 μM), LPA + PD, vehicle + SCH772984 (20 μM), or LPA + SCH for 24 h followed with or without 30-min H2O2 (0.08%) treatment, then the ROS levels were measured. g, h NSG mice were injected i.v. with 2 × 106 Ctr-KO or LPAR2-KO ARP1-luc MM cells. On day 7 after tumor inoculation, vehicle or 3 mg/kg CFZ were i.p. injected for 2 consecutive days in a week and repeated for 3 weeks. Tumor burden measured by bioluminescent imaging (g and left panel of h) and serum concentration of IgA kappa light chain (middle panel of h) and survival (right panel of h) were showed. i NSG mice were injected i.v. with 2 × 106 Ctr-KO or LPAR2-KO MM.1S-luc MM cells and treated as above. Summarized results showing tumor burden measured as bioluminescent images (left panel of i) and serum concentration of IgA lambda light chain (middle panel of i) and survival (right panel of i) of indicated mice. j, k NSG mice were injected i.v. with 2 × 106 ARP1 (j) or MM.1S (k) MM cells. On day 7 after tumor inoculation, vehicle, AT1 (0.2 mg/kg), CFZ (3 mg/kg) or CFZ + AT1 were i.p. injected for 2 consecutive days in a week and repeated for 3 weeks. Tumor burdens (left panels) and survival (right panels) were monitored. Results are shown as means ± S.E.M. *P < 0.05; **P < 0.01; ***P < 0.001; n.s., not significant

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