Globotriaosylceramide (Gb3) and heat-shock protein 70 (HSP70) are often co-localized on the cell surface of tumours and facilitates metastasis and cisplatin resistance. We hypothesized that targeting Gb3 could also inhibit HSP70 expression in non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM).Gb3 and HSP70 were co-localized on the cell surface. The glucosylceramide synthaseinhibitor DL-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (PPMP), Gb3 synthase siRNA and VT-1 reduced Gb3 and HSP70 expression, while HSP90-inhibitor 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) increased Gb3 and HSP70. The combination of 17-AAG and VT-1 had a synergistic cytotoxic effect. Cell membrane HSP70 expression in cisplatin-resistant tumour cells may be targeted through co-localized Gb3.
