Abplatin(IV) Inhibited Tumor Growth On A Patient Derived Cancer Model of Hepatocellular Carcinoma And Its Comparative Multi-Omics Study With Cisplatin
Background: Cisplatin is the most common antitumor alkylating agent of platinum(II) (Pt(II)) in clinic, however it had many side effects. It is necessary to develop low toxicity platinum(IV) (Pt(IV)) drugs. Multi-omics was frequently used to help one understand the mechanism of a certain therapy at the molecular level. Little was known about the mechanism of Pt(IV) drugs, which may be benifical for clinical translation. Methods: We developed a Pt(IV) drug of cisplatin with two hydrophobic
... tic chains and further encapsulated it with a drug carrier human serum albumin (HSA) to prepare Abplatin(IV). Transcriptomics, metabolomics and lipidomics were performed to clarify the mechanism of Pt(IV) drugs. T-test assay and fold change were used to find the differential substances.Results: We had further shown Abplatin(IV) had better tumor-targeting performance and greater tumor inhibtion rate than cisplatin. Lipidomics study showed that Abplatin(IV) might induce the changes of BEL-7404 cell membrane, and caused the disorder of glycerophospholipids and sphingolipids. In addition, transcriptomics and metabolomics study showed that Abplatin(IV) mainly disturbed more significant purine metabolism pathway than cisplatin.Conclusions: This research highlighted the development of Abplatin(IV) and the use of multi-omics to help one understand the mechanism of action of prodrugs and their DDS, which was the key to the clinical translation of them.