Anti-Tumor Study Of ADTHL And ADTSL On ASS1-Deficient Digestive Tract Tumors

BACKGROUND:Cancer remains the greatest threat to human health,in which treatment exists largely unsuccessful.Recent researches revelated,tumor cells often exhibit specific metabolic defects that distinguish them from normal cells.Some tumor cells have been shown to be auxotrophic for arginine,depletion of which leads to tumor death.Arginine deiminase,a bacterial enzyme from Mycoplasma hominus has been shown to attend this goal in argininosuccinate synthetase(ASS1)missing cancers,a rate-limiting enzyme for arginine biosynthesis,through degraded arginine.METHODS:RT-PCR were applied to measure expression levels of ASS1 in tumor cell lines.CCK8 and flow cytometric analysis assay were used to assess different biological functions affected by arginine depletion.TEM were used to explore the mechanism of arginine deprivation functions in vitro.Xenografts,immunohistochemistry and TUNEL assays are performed to evaluate tumorigenicity in vivo.RESULTS:We observed the mRNA expression of argininosuccinate synthetase(ASS1)was varied in tumor cell lines;ADI,ADTHL and ADTSL treatment induced G0/G1 phase arrest and autophagosomes formed,promoted apoptosis and suppressed Hep3 B cell proliferation in vitro,and inhibited HCC tumor growth in vivo.CONCLUSION:The arginine depletion mediated by arginine deiminase may thus be a metabolic therapy for certain tumors which is reduced expression of ASS1 and auxotrophic for arginine.