Osteosarcoma is a highly aggressive neoplasm. Traditional platinum chemotherapeutic agents for osteosarcoma inevitably have acquired drug resistance and serious side effects, which have limited their utility. To slow down the reaction of platinum drugs with glutathione (GSH) is a strategy to overcome the resistance of platinum chemotherapeutic agents. Herein, the unique design of a GSH inert bisphosphonate platinum complex cis-{di(amino)platinum[tetraethyl 2,2-bis(2-pyridinylmethyl)methylidene-1,1-bisphosphonate]} (DBPP) is reported. MTT assay demonstrates that DBPP showed moderate inhibition towards human osteosarcoma cell line U2OS cells. The cytostatic action of DBPP is related to conformational conversion from B-DNA to A-DNA and the unwinding of pUC19 DNA. DBPP could also destroy the tertiary structure of human serum albumin (HSA). Notably, 31P NMR and 1H NMR indicate that DBPP can hardly chelate with GSH, which could overcome the GSH-induced side effects. We envision that this unique design of the platinum complex would open up new ways to overcome GSH-induced resistance.

Lipid transporter protein apolipoprotein E (APOE) has contributed to functional studies of various organ functions. Animals with ApoE knockout (KO) have been used to study atherosclerosis and hyperlipidemia while an increasing number of researchers have recently focused on the association of ApoE with hearing loss. A study found that ApoE KO mice experience sensorineural hearing loss and hair cell loss, but the exact mechanism is unclear. To explore the potential relationship between ApoE and hearing loss, we used HEI-OC1 cells (House Ear Institute-Organ of Corti) with Corti apparatus properties to reveal cell changes after ApoE knockout by combined transcriptome and metabolomic analysis. We found that glutamate deficiency, caused by reduced expression of glutamine transporter proteins, was a key correlate of basal metabolism and that inadequate glutamate causes apoptosis by reducing the cells’ resistance to external damage. Our study provides a reference mechanism for hearing loss due to ApoE KO.