Licl Can Enhance Trail Anticancer Effect In Oncolytic Adenovirus Vector Or In Vivo

Background: TRAIL belongs to cancer necrosis factor-related apoptosis inducingligand, it inducts selectively cell apoptosis in tumor and transformed cells, while nokilling effect on normal cells. However, some cancer cells have low TRAIL toleranceand sensitivity, which greatly limits the TRAIL anti-cancer effect. Glycogen synthasekinase (GSK-3) is a multifunctional serine/threonine-like kinase, a key regulatoryenzyme in variety signal transduction pathways, its decomposition and suppressionhave a close contact with many difficult diseases, such as cancers, neurodegenerativediseases, Alzheimer’s disease and bipolar disorders. GSK-3inhibitor LiCl can be tosome extent. Oncolytic adenovirus EIA gene promoter is replaced by the survivinpromoter (abbreviated as sp).In this study, while carrying exogenous geneTRAIL,which is Ad.sp-E1A-E1B(△55)-TRAIL-Flag. Study its joint killing effect withLiCl on cancer cells, and the role of the process that whether they have a very goodsynergies. The implementation of this study helps to elucidate the Mecular biologicalmechanisms of tumor development, provide new Mecular targets and assessmentmaterials for future screening of tumor suppressor the drugs, and also provide atheoretical basis for future clinical prevention and treatment of malignant tumors.Objective: To study the glycogen synthase kinase3inhibitors LiCl joint killing effectwith oncolytic adenovirus carrying TRAIL(Ad.sp-E1A-E1B(△55)-TRAIL-Flag)towards cancer cells and the role of the process that whether they have a very goodsynergies.Methods: MTT assay cancer-specific virus Ad.sp-E1A-E1B(△55)-TRAIL-Flag jointdrug LiCl inhibits the proliferation of cancer cell lines; crystal violet experiment isused to observe the killing effect of the drug combination; Western Blot assay testsTRAIL expression changes in cancer cells after combination. And modeling7721nude mice transplanted liver tumor to study the joint anti-cancer effect of virus withLiCl in vivo. Results: The results indicate Ad.sp-E1A-E1B(△55)-TRAIL-Flag joint LiCl processingthree cancer cells, the inhibit efforts on proliferation was significantly better than thevirus alone, and in a certain range, with the LiCl concentration enhanced, the killingeffect is more obvious, which suggesting LiCl can promote the anti-cancer function ofTRAIL. Western Blot experiments proves LiCl improve TRAIL protein expressionlevels in the cancer cells, thereby enhancing Ad.sp-E1A-E1B(△55)-TRAIL-Flag killingeffect is by TRAIL signaling pathway. This synergy either mediated TRAIL highlyexpressed only in tumor cells, they can overcome the inherent resistance toTRAIL-induced apoptosis in hepatocellular carcinoma, which significantly improvethe virus and gene effect of killing tumor cells, which is targeted gene virus incombination with chemotherapy that opened up a new way for the treatment ofcancer.