scholarly journals A novel time-course cDNA microarray analysis method identifies genes associated with the development of cisplatin resistance

Oncogene ◽  
2004 ◽  
Vol 23 (3) ◽  
pp. 744-752 ◽  
Author(s):  
Martin A Whiteside ◽  
Dung-Tsa Chen ◽  
Renee A Desmond ◽  
Sarki A Abdulkadir ◽  
Gary L Johanning
Cells ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 143 ◽  
Author(s):  
Dessy Chan ◽  
Yuanyuan Zhou ◽  
Chung Chui ◽  
Kim Lam ◽  
Simon Law ◽  
...  

Cisplatin (CDDP) is one of the front-line chemotherapeutic drugs used in the treatment of esophageal squamous cell carcinoma (ESCC). Occurrence of resistance to CDDP has become one of the main challenges in cancer therapy. In this study, the gene expression profile of CDDP-resistant ESCC cells was investigated and molecular approaches were explored in an attempt to reverse the CDDP resistance. A CDDP-resistant SLMT-1/CDDP1R cell line was established from SLMT-1 cells by subculturing in the medium containing an increasing concentration of CDDP (0.1–1μg/mL). Mitochondrial (MTS) cytotoxicity assay, cell proliferation assay and cell morphology were used to assess the acquisition of cisplatin-resistance. The most differentially expressed gene in SLMT-1/CDDP1R cells was identified by cDNA microarray analysis compared with the parental SLMT-1 cells and validated by quantitative real-time polymerase chain reaction (qPCR). Association between expression of the most differentially expressed target gene to cisplatin-resistance was verified by RNA interference. An attempt to reversecisplatin-resistance phenotypes was made by using the vector expressing the most downregulated target gene in the CDDP-resistant cells. A CDDP-resistant ESCC cell line, SLMT-1/CDDP1R, was established with 2.8-fold increase CDDP-resistance (MTS50 = 25.8 μg/mL) compared with the parental SLMT-1 cells. cDNA microarray analysis revealed that IGFBP5 showed the highest level of downregulation in SLMT-1/CDDP1R cells compared with the parental SLMT-1 cells. Suppression of IGFBP5 mediated by IGFBP5-targeting siRNA in parental SLMT-1 cells confirmed that IGFBP5 suppression in ESCC cells would induce CDDP-resistance. More importantly, upregulation of IGFBP5 using IGFBP5 expression vector reduced cisplatin-resistance in SLMT-1/CDDP1R cells by 41%. Thus, our results demonstrated that IGFBP5 suppression is one of the mechanisms for the acquisition of cisplatin-resistance in ESCC cells. Cisplatin-resistance phenotype can be reversed by increasing the expression level of IGFBP5. The overall findings of this study thus offered a new direction for reversing the CDDP resistance in ESCC and possibly in other cancer types with further investigations in future.


2004 ◽  
Vol 5 (1) ◽  
pp. 40-58 ◽  
Author(s):  
Daniel L. E. Waters ◽  
Timothy A. Holton ◽  
Effie M. Ablett ◽  
L. Slade Lee ◽  
Robert J. Henry

Genomics ◽  
2006 ◽  
Vol 87 (1) ◽  
pp. 113-118 ◽  
Author(s):  
Camino Bermejo-Rodríguez ◽  
María Pérez-Caro ◽  
Pedro Antonio Pérez-Mancera ◽  
Margarita Sánchez-Beato ◽  
Miguel A. Piris ◽  
...  

2009 ◽  
Vol 28 (1) ◽  
pp. 10-23 ◽  
Author(s):  
Sylvia H. Trang ◽  
David E. Joyner ◽  
Timothy A. Damron ◽  
Albert J. Aboulafia ◽  
R. Lor Randall

2020 ◽  
Vol 21 (2) ◽  
pp. 472 ◽  
Author(s):  
Yuri Cho ◽  
Min Ji Park ◽  
Koeun Kim ◽  
Jae-Young Park ◽  
Jihye Kim ◽  
...  

Abstract: Background: Crosstalk between tumors and their microenvironment plays a crucial role in the progression of hepatocellular carcinoma (HCC). However, there is little existing information about the key signaling molecule that modulates tumor-stroma crosstalk. Methods: Complementary DNA (cDNA) microarray analysis was performed to identify the key molecule in tumor-stroma crosstalk. Subcutaneous xenograft in vivo murine model, immunoblotting, immunofluorescence, and real-time polymerase chain reaction using HCC cells and tissues were performed. Results: The key molecule, regenerating gene protein-3A (REG3A), was most significantly enhanced when coculturing HCC cells and activated human hepatic stellate cells (HSCs) (+8.2 log) compared with monoculturing HCC cells using cDNA microarray analysis. Downregulation of REG3A using small interfering RNA significantly decreased the proliferation of HSC-cocultured HCC cells in vitro and in vivo, and enhanced deoxycholic acid-induced HCC cell apoptosis. Crosstalk-induced REG3A upregulation was modulated by platelet-derived growth factor ββ (PDGF-ββ) in p42/44-dependent manner. REG3A mRNA levels in human HCC tissues were upregulated 1.8-fold compared with non-tumor tissues and positively correlated with PDGF-ββ levels. Conclusions: REG3A/p42/44 pathway/PDGF-ββ signaling plays a significant role in hepatocarcinogenesis via tumor-stroma crosstalk. Targeting REG3A is a potential novel therapeutic target for the management of HCCs by inhibiting crosstalk between HCC cells and HSCs.


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