Inhibitory Role of Cucurbitacin B with Polylactic Acid Nanoparticles Carrying Long Non-Coding RNA (LncRNA) Cancer Susceptibility Candidate 2c (CASC2c) in Oral Cancer Cell Migration and Invasion Through Targeting of Signal Transcription and Activator of Transcription (STAT) Signaling Pathway
SCIENCE OF ADVANCED MATERIALS(2021)
Abstract
Polylactic acid nanoparticles (PLA-NPs) not only have the characteristics of NPs, but also can be used as drug IP: 182.75.50.34 On: Thu, 03 Feb 2022 07:19:15 carriers. In this experiment, PLA-NPs were used as nano-carriers to construct nano-drugs carrying cucurbitacin Copyright: American Scientific Publishers B and long non-coding RNA (lncRNA) cancersusceptibility candidate 2c (CASC2c) (lncRNA CASC2C), to Delivered by Ingenta intervene oral cancer cells followed by analysis of their effect on cell progression. CuB-PLA-NPs and CuB-PLANPs-CASC2c were prepared, and properties of two NPs and in vitro drug release were analyzed. Oral cancer cells were treated with CuB-PLA-NPs or CuB-PLA-NPs-CASC2c. MTT was used to detect cell proliferation under intervention of 3.125, 6.25, 12.5, 25, 50, and 100 mu mol/L drug concentrations. AnnexinV/PI staining method detected cell apoptosis, and Transwell assay detected cell migration and invasion. Moreover, RT-qPCR was applied to detect expressions of CASC2C, STAT3, MMP-2, and VEGF. CuB-PLA-NPs were milky white granular, and there was no adhesion between NPs with in vitro drug release of 90% and short release time. The CuB-PLA-NPs-CASC2c (size of 200 nm) had the release rate of 62%, with long release time. The proliferation inhibition rate was increased with increased drug concentration (P < 0.05). Experimental group showed higher proliferation inhibition rate than blank and control groups (P < 0.05). Treatment with CuB-PLA-NPs-CASC2c resulted in increased apoptosis rate (90%) (P < 0.05) and decreased both cell migration rate [(49.78 +/- 33.79)%] and invasion rate [(10.24 +/- 8.79)%] (P < 0.05). Additionally, CASC2c expression (57.34 +/- 3.21) was higher in experiment group, but expressions of STAT3 (29.78 +/- 4.21), MMP-2 (10.96 +/- 291), and VEGF (29.41 +/- 4.01) all decreased (P < 0.05). CuB-PLA-NPs-CASC2c inhibited oral cancer cell migration and invasion and further increased apoptosis. The high expression status of CASC2c in oral cancer cells negatively regulates the STAT3 signaling pathway, and further inhibits expression of MMP-2 and VEGF, thus inhibiting the formation of new blood vessels.
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Key words
Cucurbitacin B,Polylactic Acid Nanoparticles,Carrier,Long Non-Coding RNA Cancer Susceptibility Candidate 2C,STAT3,Oral Cancer,Migration,Invasion
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