Project description:The aim of this study was to identify chemoresistance-associated genes in hepatocellular carcinoma (HCC). cDNA microarray analysis was performed to compare the mRNA expression profiles of a human metastatic HCC cell line (named MHCC97Low) and its derived chemoresistant sublines including cisplatin resistant subline (named MHCC97L/CisR or C8) and doxorubicin resistant subline (named MHCC97L/DoxR or D5). Total RNAs were extracted from MHCC97Low (97Low as sample name), MHCC97L/CisR (C8 as sample name) and MHCC97L/DoxR (D5 as sample name), and hybridized on Affymetrix microarrays. We planed to identify differential genes between 97Low and C8 (cisplatin resistant genes) as well as to identify differential genes between 97Low and D5 (doxorubicin resistant genes).
Project description:The aim of this study was to identify chemoresistance-associated genes in hepatocellular carcinoma (HCC). cDNA microarray analysis was performed to compare the mRNA expression profiles of a human metastatic HCC cell line (named MHCC97Low) and its derived chemoresistant sublines including cisplatin resistant subline (named MHCC97L/CisR or C8) and doxorubicin resistant subline (named MHCC97L/DoxR or D5).
Project description:The transcriptomic profiles of two resistant (HT and OCI-LY3) and two sensitive (SUDHL5 and OCI-LY19) DLBCL cell lines before and after doxorubicin treatment were analysed by RNA-seq. To further investigate the molecular basis underlying the development of doxorubicin resistance, acquired doxorubicin-resistant cells (OCI-LY19R) were generated by periodically treating the parental doxorubicin-sensitive OCI-LY19 cells (OCI-LY19S) with increasing doses of doxorubicin over a prolonged period till its IC50 exceeded 200 nM. RNA-seq analysis was then performed using OCI-LY19R and OCI-LY19S cell lines to examine the transcriptomic changes following acquisition of doxorubicin resistance.
Project description:We analysed aquired chemotherapeutic resistance of two different triple negative breast cancer cell lines BT-549 (Doxorubicin resistance) and MDA-MB-468 (5-Fluorouracil) by comparing the proteome of the parental cell line with the resistant cell line.
Project description:Transarterial chemoembolization or systemic chemotherapy with doxorubicin has been the treatment of choice for unresectable hepatocellular carcinoma (HCC) conferring the best survival benefit. However, HCC is notorious for its predisposition to develop therapeutic tolerance. Thus, Affymetrix microarray analysis was performed on doxorubicin-resistant hepatoma cells to identify the drug resistance-related genes. The RNA isolated from primary hepatoma cells and their doxorubicin-resistant counterparts, then subjected to Affymetrix microarray analysis to identify the differential expression profiles of drug resistance-related genes.
Project description:Resistance to lenvatinib remains an important limitation in the treatment of hepatocellular carcinoma (HCC). In this study, six patient-derived HCC organoid lines were established and classified as lenvatinib-sensitive or lenvatinib-resistant according to their ex vivo drug responses. The organoids retained histological and immunophenotypic features of their matched parental tumors. Lenvatinib-sensitive organoids exhibited more pronounced morphological changes and reduced ATP activity at higher lenvatinib concentrations, whereas ATP activity remained largely unchanged in resistant organoids. Transcriptome sequencing identified 408 upregulated and 269 downregulated genes in lenvatinib-resistant compared with lenvatinib-sensitive organoids, with HIF-1 signaling among the altered pathways. In resistant organoids, lenvatinib increased HIF-1alpha, ANGPT2, and HK3 mRNA expression, whereas comparable changes were not detected in sensitive organoids. KC7F2 reduced the lenvatinib-associated increases in these transcripts and further decreased ATP activity when combined with lenvatinib in resistant organoids. In organoid-derived xenografts, the combination of lenvatinib and KC7F2 resulted in the greatest reduction in tumor growth and lower HIF-1alpha, ANGPT2, and HK3 mRNA expression than lenvatinib alone. These findings indicate that HIF-1 signaling contributes to the lenvatinib-resistant phenotype in patient-derived HCC organoids and that its inhibition may enhance the response to lenvatinib.
Project description:The Wilms´ tumor 1 gene (WT1) encodes a transcription factor involved in cell growth and development. As we previously reported WT1 expression is hardly detectable in normal hepatic tissue but is induced in liver cirrhosis. Although WT1 has been found to be overexpressed in a number of malignancies, the role of WT1 in hepatocarcinogenesis has not been clarified. We found that WT1 is expressed in several human hepatocellular carcinoma (HCC) cell lines including PLC/PRF/5 and HepG2, and in HCC tumor tissue in 42% of patients. WT1 small interfering RNAs did not affect proliferation rate of HCC cells but abrogated their resistance to anoikis. Transcriptome analysis of PLC/PRF/5 cells after WT1 knockdown demonstrated upregulation of 251 genes and downregulation of 321. Ninety per cent of the former corresponded to metabolic genes mostly those characterizing the mature hepatocyte phenotype. On the contrary, genes that decreased upon WT1 inhibition were mainly related to defense against apoptosis, cell cycle and tumor progression. In agreement with these findings WT1 expression increased the resistance of liver tumor cells to doxorubicin, a compound used to treat HCC. Interestingly, doxorubicin strongly enhanced WT1 expression in both HCC cells and normal human hepatocytes. Among different chemotherapeutics, induction of WT1 transcription was restricted to topoisomerase 2 inhibitors. When WT1 expression was prohibited doxorubicin caused a marked increase in caspase-3 activation. In conclusion, WT1 is expressed in a substantial proportion of HCC contributing to tumor progression and resistance to chemotherapy, suggesting that WT1 may be an important target for HCC treatment. Keywords: Cell type comparison