Further Study On Tongue Cancer Resistance-associated Gene(TCRP1) Specifically Mediated Chemoresistance To Platinum Anti-cancer Agents

Background and AimTongue cancer resistance-associated gene (TCRP1) was cloned in tongue cancer multi-drug resistance cell Tca8113/PYM in our earlier research. TCRP1, regulated by translation factor c-MYC,can specificity mediated tongue cancer cells cisplatin and radiation resistance via AKT/NF-KB and some else antiapoptotic pathways both in vivo and vitro.Meanwhile, not only in tongue cancer,TCRP1also high expression in lung cancer,ovarian cancer,breast cancer and kinds of organization than those normal tissue,which point out that TCRP1gene can mediate platinum tolerance in wide variety tumor.To prove this hypothesis,this study was to test the relationship of TCRP1gene and the srcondary platinum tolerance in the above tumor; and the correlation of primary platinum resistance and TCRP1in a serious of lung cancers. Providing further evidence to determine the symbol function of TCRP1mediated platinum tolerance and carry out TCRP1as prediction and intervention target in chemotherophy tolerance.Methods(1)We detecting the drug sensitivity of platinum drugs(cisplatin cDDP and oxaliplatin L-OHP) and those correlation with TCRP1genes expression by MTS, QPCR and Western Blot in ovarian cancer(COC1,COC1/DDP),lung cancer(A549,A549/DDP), as the positive control cisplatin resistance cell Tca8113/PYM and negative control cisplatin sensitive cell MCF-7/5-FU.(2) We screening cisplatin primary resistant and sensitive cells from8lung cancer cells by MTS, and find the relevancy of cisplatin resistance and TCRP1gene expression by QPCR and Western Blot.(3) SI-RNA interference TCRP1and c-MYC gene in above acquired and congential resistance cells,Bay11-7082inhibit NF-κB in above cells. MTS and Western Blot detect changes of platinum drugs sensitivity and related singal molecular after processing.Verify the regulation of c-MYC to TCRP1, and the mechanism of TCRP1mediated platinum drug toleranceResults(1) TCRP1gene was significantly high expression in COC1/DDP, A549/DDP and Tca8113/PYM than those parent cells.while there wasn’t any obvious difference in MCF-7/5-FU and its parent cell TCRP1high expression cell lines was obvous insensitive to platinum drug (cDDP and L-OHP) than those lower expression cells.There is a positive relationship between them (rcDDP=0.67,rL-OHP=0.83;p<0.05).(2)There is a positive relationship between TCRP1gene expression and the cisplatin resistance in8kinds of lung cancer cells (r=0.68; p<0.05).Among them the cDDP and L-OHP resistance in the highest expression of TCRP1cell95D increased respectively5.5,5.6fold than the lowest H1299.(3) After interference the TCRP1, NF-κB and c-MYC genes in acquired drug resistance cells (COC1/DDP, A549/DDP,Tca8113/PYM) and congential drug resistance cell95D,those resistance to platinum all got a certain degree reversal. c-MYC can be used as the regulation of gene TCRP1which mediated the platinum drugs resistance through AKT/NF-κB/Bcl-2signal pathways.Conclusions(1) TCRP1gene not only mediated the chemotherapy resistance in tongue cancer,but also in lung cancer,ovarian cancer and else kinds of cancer.(2) TCRP1gene not only mediated the secondary tolerance in chemotheraphy, but also mediated the primary resistance.(3) TCRP1gene not only mediated cisplatin chemotherapy resistance,but also mediated oxaliplatin resistance.