Relationship Between Bystander Effect Of Suicide Gene Therapy Enhanced By All-Trans Retinoic Acid In Prostate Cancer And Connexin43 Protein

It is lack of effective therapies for prostate cancer at advanced stage now. Gene therapy is one of the most promising treatments which can cure prostate cancer and become the most important part of compositive treatment. The etiology of prostate cancer is the result of a few stages of dedifferentiation and the accumulation of genes' mutation. Prostate cancer is located in the prostate only, fit to puncture according to it's anatomy, and has sepecific tumor marks which are prone to follow-up.So prostate cancer is fit for local gene therapy , and has been recently reported to be cured or relieved significantly with it.Herpes simplex virus thymidine kinase(HSV-TK)/ganciclovir(GCV ) system is the gold standard for other suicide gene therapies. HSV-TK gene, along with which tabled with tissue specific gene promoter or immune factors' genes, has been used effectively and widely to treat prostate cancer since 1990s. The most important mechanism of HSV-TK/GCV against tumors is by-stander effect(BSE), which has been made sure in the fact that only 10% TK~+ tumor cells could kill all the TK" cell around. The BSE is based on gap junction(GJ) among same cells. GJ is made up of six same membrane connexins(Cx) . Prostate tissue mainly expresses Cx43. When Cx located in kytoplasm or expressed lowly, functional GJ could not be composed. GJ can transfer energy and information among cells and mediate intercellular communication(GJIC) that controls differentiation and growth of normal cells. It appeares that normal cells might grow , proliferate and differentiate abnormally if the GJIC was low or lack. The inefficacy of HSV-TK/GCV system against tumors would result in low TK gene transfection rate or/and bad BSE. The rate of TK transfection could be boosted by using proliferous adenovirus. The BSE could be also increased by Cx gene transfection or using chemical medicines which could induce the expression of Cx. Because of low rate of gene transfection nowaday, chemical inductors, such as retinoid, cAMP, glucocorticoid,...