Efficient treatment of colon cancer with codelivery of TRAIL and imatinib by liposomes.

Abstract：Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce apoptosis by interacting with death receptors. However the short half-life and the resistance of tumor cells to TRAIL limit its therapeutic effect. Imatinib has been shown to be effective against colon cancer cell lines and enhance TRAIL-induced apoptosis. However the side effects of it were unavoidable during treatment. To solve these problems, we successfully prepared a kind of multifunctional liposome that encapsulated imatinib in its internal water phase and inserted TRAIL on its membrane in this study, which named ITLPs. The liposomes appeared uniform spherical and the particle size was approximately 150 nm. ITLPs showed high accumulation in TRAIL-resistance cells and HT-29 tumor-bearing mice model. In vitro cytotoxicity assay results showed that the killing activity of HT-29 cells treated with ITLPs increased by 50% and confirmed that this killing activity was mediated by the apoptosis pathway. Through mechanism studies, it was found that up to 32.3% of cells were arrested by ITLPs in phase M to exert anti-tumor effects. In vivo anti-tumor study showed that ITLPs achieved 61.8% tumor suppression and little toxicity in the HT-29 tumor-bearing mice model. Overall results demonstrated that codelivery of imatinib and TRAIL via liposomes may be a prospective method in the treatment of the TRAIL-resistance tumor.