Bladder cancer is a common malignancy in the urinary system. Defects of drug molecules in bladder during treatment, such as passive diffusion, rapid clearance of periodic urination, poor adhesion and permeation abilities, lead to low delivery efficiency of conventional drugs and high recurrence rate of disease. In this study, we designed multi-responsive mesoporous polydopamine (PDA) composite nanorods cooperating with nano-enzyme and photosensitiser for intensive immunotherapy of bladder cancer. The strongly adhesive mesoporous PDA with wheat germ agglutinin on nanoparticles could specifically adhere to epithelial glycocalyx and made the nanoparticles aggregate in urinary pathways. Meanwhile, 2,3-dimethylmaleic anhydride could be hydrolysed in acidic conditions of tumour microenvironment, giving it a positive charge (charge reversal), which is more amenable to enter cancer cells.Afterwards, manganese dioxide nanorods could catalyse the reaction of excess H 2 O 2 in tumour microenvironment to generate active oxygen, so as to change the hypoxic environment in tumour, and achieve a pH-responsive for slow release of PD-L1. After the ICG was irradiated by infrared light, a large amount of singlet oxygen was generated, thereby enhancing the therapeutic effect and reducing toxicity in vivo. Besides, mesoporous PDA with indocyanine green photothermal agent could have a local heat up quickly under the near-infrared light to kill cancer cells, thereby enhancing therapeutic efficacy. Accordingly, this mesoporous PDA composite nanorods shed a light on bladder tumour treatment.
Purpose
Our goal was to investigate the effect of
SMYD3
on the biological behavior and histone 3 lysine-4 (H3K4) methylation of bladder cancer (BLAC).
Patients and methods
qRT-PCR identified that
SMYD3
expression level in BLAC cell lines (T24, 5637, BUI-87 and J-82) and human normal uroepithelial cell line SV-HUC1. We also constructed green fluorescence protein lentiviral vector using the gene short hairpin RNA (shRNA) system. We used Western blot to analyze the
SMYD3,
H3K4me1, H3K4me2 and H3K4me3 expression levels in shRNA transfection lines. We also performed a colony-forming assay to determine colony-forming ability, cell counting kit-8 for cell proliferation detection, Transwell assay to determine cell migration and invasion and Annexin V-FITC/PI double staining to analyze cell apoptosis.
Results
The
SMYD3
expression level was significantly higher in BLAC cell lines (T24, 5637, BUI-87 and J-82) than in human normal uroepithelial cell line SV-HUC1, and exhibited the highest expression level in T24 cells, among the cell lines tested. qRT-PCR and Western blot analysis results showed that
SMYD3
was successfully suppressed in shRNA transfection lines, and identified that
SMYD3
suppression resulted inhibited H3K4me2 and H3K4me3 but not H3K4me1.
SMYD3
knockdown cells accelerated cell apoptosis and exhibited low cell colony-forming ability, proliferation ability, inhibition of cell migration and invasion compared with normal cells.
Conclusion
SMYD3
may be activated in BLAC cells to increase H3K4 activity to modulate cell proliferation, migration and invasion ability. The data will be a useful source for future therapy.
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