IADR Abstract Archives
CaCO3-Based Nanoparticles Incorporating Plasmid Encoding miR-200c Inhibit OSCC Growth
Objectives: Oral squamous cell carcinoma (OSCC) is the most prevalent head and neck cancer with high recurrences, metastasis, and mortality rates even after curative treatment. MicroRNAs (miRs) are small non-coding RNAs that regulate pathophysiological processes, including OSCC initiation and progression. Specifically, miR-200c is reported to regulate aspects of OSCC progression, including the epithelial-mesenchymal transition, and cancer cell migration and invasion. This study investigates the inhibitory function of plasmid DNA encoding miR-200c delivered via CaCO3-based nanoparticles on tumor growth in vitro and in vivo.
Methods: OSCC cells were transfected with pDNA encoding miR-200c via CaCO3-based nanoparticles. OSCC cell proliferation, migration, motility and associated oncogene production were quantified using MTT assay, scratch assays and qRT-PCR. We further investigated the in vivo tumor growth of OSCC cells with miR-200c overexpression. Expression of OSCC-associated oncogenes in the tumors was measured using qRT-PCR and immunohistochemistry. We also tested the inhibitory activities of miR-200c on tumor growth of OSCC cells in a mouse model by local administration of pDNA encoding miR-200c delivered using CaCO3-based nanoparticles.
Results: miR-200c transfection using CaCO3 significantly reduces OSCC cell proliferation compared to controls and the CaCO3: protamine sulfate ratio influences transfection efficiency. OSCC cells overexpressing miR-200c significantly lower proliferation and migration, and downregulate OSCC markers (CCND1, CDKN2A, FADD, FAT1, NOTCH1, P53 and PIK3CA) in vitro and in vivo and decrease in vivo tumor size compared to controls. Furthermore, local application of miR-200c delivered via CaCO3-based nanoparticles enhances miR-200c transfection and significantly suppresses tumor growth by OSCC cells in mice.
Conclusions: These results demonstrate the ability of miR-200c to suppress OSCC proliferation and migration. Our CaCO3-based nanoparticles enhance miR-200c transfection and may serve a novel treatment to reduce oral cancer recurrence.
Methods: OSCC cells were transfected with pDNA encoding miR-200c via CaCO3-based nanoparticles. OSCC cell proliferation, migration, motility and associated oncogene production were quantified using MTT assay, scratch assays and qRT-PCR. We further investigated the in vivo tumor growth of OSCC cells with miR-200c overexpression. Expression of OSCC-associated oncogenes in the tumors was measured using qRT-PCR and immunohistochemistry. We also tested the inhibitory activities of miR-200c on tumor growth of OSCC cells in a mouse model by local administration of pDNA encoding miR-200c delivered using CaCO3-based nanoparticles.
Results: miR-200c transfection using CaCO3 significantly reduces OSCC cell proliferation compared to controls and the CaCO3: protamine sulfate ratio influences transfection efficiency. OSCC cells overexpressing miR-200c significantly lower proliferation and migration, and downregulate OSCC markers (CCND1, CDKN2A, FADD, FAT1, NOTCH1, P53 and PIK3CA) in vitro and in vivo and decrease in vivo tumor size compared to controls. Furthermore, local application of miR-200c delivered via CaCO3-based nanoparticles enhances miR-200c transfection and significantly suppresses tumor growth by OSCC cells in mice.
Conclusions: These results demonstrate the ability of miR-200c to suppress OSCC proliferation and migration. Our CaCO3-based nanoparticles enhance miR-200c transfection and may serve a novel treatment to reduce oral cancer recurrence.