The Effects Of Suppressing GPR87on Sensibility To Cisplatin And Pirarubicin In Bladder Cancers

Backgroud：Bladder carcinoma is a common malignancy in urinary system.Resistance to Cisplatin and Pirarubicin in bladder cancer patients is moreand more severe today, simultaneously accompanying the growth of drugside-effect.Thus, elucidating mechanisms of resistance to these drugs willimprove the sensitivity to chemotherapy to further maximize clinicalbenefit.Idea of research：It has been proved that wild type P53gene can induce GPR87expression in colon cancer cells ongoing DNA damage. Inhibition ofGPR87expression can sensitize colon cancer cells to drugs related withDNA damage. Due to high expression of GPR87in bladder cancers,we candeduced that GPR87gene is also associated with drug resistance in bladdercancer, shRNA plasmids were constructed to intefere with GPR87expression in bladder cancer cells to test whether bladder cancer cells aremore sensitive to Cisplatin and Pirarubicin when decreasing the expression of GPR87. Our aims were reducing drug doses and improving treatmenteffects of bladder cancer.Main results and conclusion：1. Result: BIU87cells showed significant damage responses whentreated with2μg/ml Cisplatin,0.25μg/ml Pirarubicin, and1μg/mlCisplatin and0.125μg/ml Pirarubicin for24h, respectively. T24cellsshowed significant damage responses when treated with at4μg/mlCisplatin,1μg/ml Pirarubicin,2μg/ml Cisplatin and0.5μg/ml Pirarubicin24h,respectively.Conclusion： BIU87cells and T24cells showed significant damagesunder the optimum concentration of drugs.2. Results：P53and GPR87mRNA and protein level were increasedfollowing Cisplatin、 Pirarubicin and combined treatment for24hrespectively in BIU87cell(P<0.05). P53and GPR87mRNA and proteinlevel showed no significant changes following Cisplatin,Pirarubicin andCisplatin/Pirarubicin combination for24h respectively in T24cells(P>0.05).Conclusion：GPR87can be upregulated by P53in BIU87cell. GPR87can not be regulated by P53in T24cell.3. Results: BIU87cell transfeceted with GPR87-1plasmid weresusceptible to Cisplatin、Pirarubicin and combined treatment,increaseing incell apotosis related protein P53,P21,MDM2,PARP expression(P<0.05) and have significant apotosis changes in nucleus morphology.T24cells weretransfected with GPR87-1plasmid showed no siginificant changes insusceptibility to cisplatin and pirarubicin and combined treatment andincreaseing in cell apotosis related protein P53,P21,MDM2,PARPexpression(P>0.05) and didn’t have significant apotosis changes in nucleusmorphology.Conclusion: GPR87gene plays an important role in sensibity toCisplatin、Pirarubicin in bladder cancers...