Study On The Relationship Between Aurora A Expression And The Growth And Invasive Ability Of Cancer Cell And Treatment Efficacy Of Taxol For Prostate Cancer

BackgroundAurora A is an important member of the Aurora kinase family, which was firstly detected from the tissue of breast cancer.It was named by BTAK (breast tmnouractivated kinase),Aurora 2,AIK1(Aurom/Ipll kinase),STK15(serine/threonine kinase 15),STK6(serine/threonine kinase 6,HsAIRKl(Aurora/Ipll related kinase). Aurora A kinase is made of 403 amino acid,whose construction accord with the common rule of the family. The N terminal has 3 Aurora box,which could have relationship with the orientation of Aurora A in the cells and with the identification and combination of the other proteins. Recently,it was proved that Aurora A box 2 could depolymerize with the D-box of N terminal. And Aurora A could regulate mitosis of cells by regulating the function of centrosome, canaliculus and spindle. Abnormal up-regulated expression of Aurora A kinase could arouse the error of cells mitosis,and accordingly induce heteroploidy and increase of the copy number of chromosome.As a result of that,it could place a premium on malignant transform of cells. Our foregoing research results showed that Aurora A mRNA was over expressed in 91% of the prostate cancer tissue,and the expression of Aurora A was up regulated in 86 % of the prostate cancer sample,while there was no expression of Aurora A in the normal tissue.In addition to that,we still found Aurora A mRNA and expression of Aurora A were all up regulated in the three cell species: PC3, LNCaP and Du145.It was revealed that Aurora A was related to the forming of prostate cancer.The osculation relationship between Aurora A and tumour has been approved in many cancers,but the relationship between up-regulated expression of Aurora A and occurrence and development of prostate cancer has not been reported.Prostate cancer is a commom malignant tumour of reproductive system of males. Incidence of the disease is low in our country,but it is detected in metaphase or aftermoon.And there is an uptrend of incidence of the disease in the recent years. Endocrinotherapy is a common treatment of prostate cancer.But chemotherapy is the main treatment for the hormone-independent prostate cancer now,whose treatment efficacy is not well-pleasing.Taxane has the predominance on the treatment of hormone-independent prostate cancer in recent years and it has a good application future.With the deeply research,it was found that treatment efficacy of taxane could regulated by many factors,and accordingly the resistance to drug can be aroused.The main mechanism of taxol to treat the cancer is to inhibit the depolymerization of canaliculus. Usually, the canaliculus is polymerized with the help of GTP and canaliculus binding protein and it is affected withβ- canaliculus protein.Taxol can be combined toβ- canaliculus protein firstly,and accordingly result in the convergence of canaliculus in the place where there is a lack of GTP and the other protein assistant factors.On the condition of taxol, polymeric canaliculus can be centralized.The homeostasis of canaliculus is destroyed by static convergence and accordingly canaliculus lose the functions. As a result of that, chromosome centromere of cells ,canaliculus linker and canaliculus strain could be out of the way,which activate the mitosis check area.It was indicated by the research that Mad2 and Bub1 were the main numerators to apperceive the singularity of canaliculus linker and canaliculus strain.The target of their action is celldivision control protein(cdc20),which can activate an anaphase promoting complex(APC).The active APC decomposes regulation protein securin,and then the securin activates separating enzyme separase which can decompose cohesin. Cohesin is a complex protein that can connect the sister chromosome monomer.The decomposing of cohesin could separate the sister chromosome monomer,and accordingly cells come into the anaphase from the metaphase. When mitosis check area is activated, Mad2 and Bub1 are combined to CDC20,which can inhibit the activation of APC.Accordingly, cohesin cannot be decomposed normally and sister chromosome monomer cannot be separated normally.Then,the cell cycle stagnates in the metaphase and it arouses the apoptosis. Therefore,the sensitivity of taxol must depend on the mitosis check area which has an intact function.It was found in the recent years that over expression of Aurora A could get across the mitosis check area,which can induce the resistance of Hela.to taxol. Our foregoing research showed that transcription and translation of Aurora A were up regulated in the tissue and cells (PC3,Du145,LNCap)of prostate cancer. Aurora A up-regulated expression can strengthen the growth and invasive ability of cancer cell,which showed that Aurora A may play an important role in the occurrence and development of prostate cancer.But up to now,there is not any report about the relationship between over expression of Aurora A and resistance to drug of prostate cancer cell.In this research,we made use of prostate cancer cell LNCaP as the research object,which has a low Aurora A espression. The growth and proliferation of the cells were detected by MTT and the mobility of cells was examined by transwell cell layer infiltration assay.The growth and motility of LNCaP- Aurora A cells were compared with those of the LNCaP-pcDNA3.1 and LNCaP cells in order to examine the effect of Aurora A in the carcinogenesis of prostate cancer.In addition to that,we discussed the relationship between the expression of Aurora A and the effect of Taxol for prostate cancer to reveal that the expression of Aurora A is related to the treatment efficacy of Taxol for prostate cancer,and generate the theory evidence to improve the treatment efficacy of Taxol for prostate cancer.Methods1. The growth and prilferation of the LNCaP-Aurora A,LNCaP- pcDNA3.1 and LNCaP cells were detected by MTT.2. The invasion ability of the LNCaP-Aurora A,LNCaP-pcDNA3.1 and LNCaP cells was examined by transwell cell layer infiltration assay.3. Du145 cells and Du145-Aurora A cells were treated with differrent dose taxols. The growth inhibition rate of cells were detected by MTT assay,and the cell apoptosis rate was detected through flow cytometry. Then,the cell growth inhibition rate and cell apoptosis rate ofDu145-Aurora A and Du145 were compared simutanously.4. Du145-Aurora A cells were treated with DNAzymes to down-regulate the Aurora A expression, the variation of cell growth inhibition rate and cell apoptosis rate were detected.Results1. Compared to the LNCaP- pcDNA3.1 and LNCaP cells,the cells with highexpression of Aurora A had faster prliferation.2. Compared to the LNCaP- pcDNA3.1 and LNCaP cells,the cells with highexpression of Aurora A had stronger invasion ability.3. Up-regulation of Aurora A reduces cell inhibition rate and apoptosis ratewhen treated by taxol.4. Down-regulation of Aurora A increases cell inhibition rate and apoptosis rate when treated by taxol.Conclusions1. The increased expression of Aurora A is closely associated with the malignant phenotypes of prostate cancer. Aurora A may play a very important role in the carcinogenesis of prostate cancer.2. There is a positive relationship between Aurora A expression andtreatment efficacy of taxol for prostate cancer, and inhibition of Aurora A will enhance the treatment efficacy of taxol for prostate cancer.