Three dimensional (3D) culture has gradually become a research hotspot in the field of drug screening, stem cell research, and tissue engineering due to its more physiological-like morphology and function. In this study, we compared the differences of cell proliferation, population, protein expression and chemoresistance profiles between two dimensional (2D) and 3D culture of acute lymphoblastic leukemia (ALL) Jurkat cell line. Polycaprolactone (PCL) is used for 3D culture owing to its biochemical properties and compatibility. Culturing of ALL Jurkat cell line in collagen type I coated polycaprolactone scaffold for 168 h increased cell proliferation, attachment, as well as the drug resistance to cytarabine (Ara-C) and daunorubicin (DNR) without changing the original CD2+CD3+CD4+dimCD8-CD34-CD45+dim phenotype, compared to uncoated PCL scaffold and tissue culture plate systems. Molecularly, increased chemoresistance is associated with the upregulation of discoidin domain receptor 1 (DDR1) and transcription factor STAT3. Inhibition of DDR1 activity by DDR1-specific inhibitor DDR-IN-1 accelerated cell death in the presence of Ara-C, DNR or their combination. These results demonstrated that 3D culture enhances chemoresistance of ALL Jurkat cell line by increasing DDR1 expression. Importantly, the cell adhesion-mediated drug resistance induced by DDR1 in the scaffold was similar to the clinical situation, indicating the 3D culture of cancer cells recapitulate the in vivo tumor environment and this platform can be used as a promising pre-clinic drug-screen system.

Pancreatic carcinoma (PC) is a rapidly progressive, fatal malignant tumor with the poorest prognosis among all major carcinoma types. MicroRNAs (miRNAs/miRs) have been indicated to be key post-transcriptional regulatory factors, which are involved in cancer development. The present study was designed to investigate the effect of miR-23a on PC cell proliferation, metastasis and apoptosis. The expression of miR-23a was detected in a normal pancreatic ductal epithelial cell line and three PC cell lines, and miR-23a inhibitor or mimics were transfected into the Panc-1 and MiaPaCa2 PC cells. The association between miR-23a and tissue factor pathway inhibitor (TFPI)-2 was examined using a luciferase reporter assay. MTT and flow cytometry assays were used to assess cell viability and apoptosis, respectively. Furthermore, wound-healing, Transwell and Matrigel assays were used to evaluate cell migration and invasion abilities, and the protein expression level of TFPI-2 was determined using western blot analysis. The results of the present study revealed that miR-23a was upregulated in PC cells. Furthermore, TFPI-2 was identified as a downstream target of miR-23a, and TFPI-2 expression was found to be increased following miR-23a knockdown. In addition, functional assays revealed that downregulation of miR-23a decreased PC cell proliferation, migration and invasiveness and promoted cell apoptosis, while miR-23a overexpression exerted the opposite effects. Furthermore, TFPI-2 knockdown rescued the biological effects on PC cells, which were induced by miR-23a knockdown. The results of the present study indicated that miR-23a negatively modulated TFPI-2 expression in vitro and enhanced the malignant phenotypes of PC cells. Therefore, miR-23a may be a potential marker and/or target for the diagnosis and treatment of PC.