Study On Acquired Drug Resistance Of Human Cervical Cancer Hela Cells Doxorubicin Based On Transcriptome Sequencing

Globally,the incidence of cervical cancer is lower than that of breast cancer.It ranks second among female cancers and greatly damages women's,health.Chemotherapy is currently one of the most common treatment options for cervical cancer,especially in the treatment of advanced cervical cancer.As an efficient broad-spectrum anti-cancer drug,adriamycin alone or in combination with other anti-cancer drugs has a good effect in the treatment of cervical cancer and is a potent chemotherapeutic agent.The phenomenon of tolerance to adriamycin produced during chemotherapy is one of the crucial factors affecting the cure rate of chemotherapy patients,But its molecular mechanism has not been fully determined.Therefore,this subject uses human cervical cancer He La cells and Hela/Dox cervical cancer adenocarcinoma cells constructed in vitro as a test model,using transcriptase sequencing technology on cervical cancer Hela cells and their corresponding adriamycin-resistant cells Hela/ Dox was sequence to obtain the differentially expressed genes between the two transcripts.Combined with the annotation results of the three major databases of GO,COG and KEGG and related literature,the gene function and structure in the cell can be achieved comprehensively.Target genes and signal pathways associated with acquired drug resistance of cervical cancer doxorubicin,thereby screening out molecular targets in the development of cervical cancer adriamycin resistance.Finally,we used RNA interference technology to knock down the genes associated with cervical cancer adriamycin resistance and further confirm the role of this target in acquired drug resistance to doxorubicin.A total of 2562 differential genes were obtained through transcriptase sequencing,of which 1269 genes were up-regulated in Hela/Dox cell samples and 1293 genes were down-regulated in Hela/Dox cell samples.And KEGG's annotation results showed pathways in cancer,P13K-Akt,MAPK,HTLV-1 infection pathway,Rap1,Proteoglycans in cancer,etc.were the most abundant pathways for the enrichment of differential genes.It is estimated that these signaling pathways may be involved in human cervical cancer adriamycin resistance.Drug formation process.We selected genes with a gene expression differential multiple in the top 100.Corresponding to the KEGG pathway,we found that only 39 genes can be allocated to the corresponding pathways.After reviewing the literature,we found that the WNT10 B gene may be associated with human cervical cancer.Hela cell doxorubicin resistance mechanism is related.Therefore,we chose the WNT10 B gene as the main research object for subsequent experiments.After knocking down the Wnt10 B gene in the Hela/Dox cell line with interfering RNA,the drug sensitivity of Hela/Dox cells to doxorubicin was considerably enhanced,and The resistance index(RI)of Hela/Dox cells before and after knockout is 1.37,which had some mitigation effect on its drug resistance.The above results shows that Wnt10 B gene plays a critical role in controlling the drug resistance of Hela cells to adriamycin,laying a theoretical foundation for the chemotherapy resistance of cervical cancer,and also provides a new direction for the precise treatment of cervical cancer.