Purpose: Recent studies indicate that pregnancy upregulated non-ubiquitous calmodulin kinase (PNCK) is significantly up-regulated in breast and renal carcinomas. However, the expression profile and its biological relevance of PNCK in nasopharyngeal carcinoma (NPC) have not been elucidated.Methods: The expression level of PNCK was detected in specimens of NPC (n=10) and normal tissues (n=10) by real-time PCR and immunohistochemistry. Celigo Cell Counting and MTT assay were used to measure cell viability. Apoptosis was detected by flow cytometric analysis and caspases 3/7 activity assay. Real-time PCR and Western blotting were performed to evaluate the expression of PNCK. The bioluminescence imaging was used to evaluate the effects of PNCK knockdown on tumor growth using a xenograft animal model. The global gene expression profile was determined in wild type and PNCK-depleted CNE-2 cells via transcriptomics analysis. For mechanical investigation, the changes of PI3K/AKT/mTOR signaling pathway were detected by Western blotting.Results: The mRNA and protein levels of PNCK were increased in human NPC samples. In vitro experiments showed that shRNA or CRISPR-Cas9 mediated silencing of PNCK inhibited proliferation and induced apoptosis in NPC cells. In addition, in vivo assay revealed that knockdown of PNCK suppressed tumor growth. Consistently, a significant reduction of tumor bioluminescence in mice inoculated with PNCK-knockdown cells compared to that of control cells. In gene expression, the transcriptomics analysis revealed that there were 589 upregulated genes and 589 downregulated genes in PNCK-knockdown cells. Ingenuity Pathway Analysis (IPA) identified significant changes of PI3K/AKT/mTOR signaling pathway in PNCK-knockdown cells. Furthermore, western blot analysis revealed that interference with PNCK reduced the phosphorylation levels of PI3K, AKT and mTOR in CNE-2 cells.Conclusion: This study for the first time demonstrates that knockdown of PNCK could suppress growth and induce apoptosis of NPC cells both in vitro and in vivo by regulating PI3K/AKT/mTOR signaling pathway. These findings suggest that PNCK might be a novel therapeutic target for NPC treatment.
Nanotechnology has shown a revolution in cancer treatments,
including
breast cancers. However, there remain some challenges and translational
hurdles. Surgery, radiotherapy, and chemotherapy are the primary treatment
methods for breast cancer, although drug combinations showed promising
results in preclinical studies. Herein we report the development of
a smart drug delivery system (DDS) to efficiently treat breast cancer
by pyroptosis–starvation–chemotherapeutic combination.
Cancer-starvation agent glucose oxidase was chemically attached to
synthesized iron oxide nanoparticles which were entrapped inside poly(lactic-co-glycolic acid) along with apoptosis-associated speck-like
protein containing a caspase recruitment domain plasmid and paclitaxel
(PTX). An emulsion solvent evaporation method was used to prepare
the DDS. The surface of the DDS was modified with chitosan to which
aptamer was attached to achieve site-specific targeting. Hence, the
prepared DDS could be targeted to a tumor site by both external magnet
and aptamer to obtain an enhanced accumulation of drugs at the tumor
site. The final size of the aptamer-decorated DDS was less than 200
nm, and the encapsulation efficiency of PTX was 76.5 ± 2.5%.
Drug release from the developed DDS was much higher at pH 5.5 than
at pH 7.4, ensuring the pH sensitivity of the DDS. Due to efficient
dual targeting of the DDS, in vitro viability of 4T1 cells was reduced
to 12.1 ± 1.6%, whereas the nontargeted group and free PTX group
could reduce the viability of cells to 29.2 ± 2.4 and 46.2 ±
1.6%, respectively. Our DDS showed a synergistic effect in vitro and
no severe side effects in vivo. This DDS has strong potential to treat
various cancers.
Surface-enhanced Raman spectroscopy (SERS) was employed to detect deoxyribose nucleic acid (DNA) variations associated with the development of nasopharyngeal carcinoma (NPC). Significant SERS spectral differences between the DNA extracted from early NPC, advanced NPC, and normal nasopharyngeal tissue specimens were observed at 678, 729, 788, 1337, 1421, 1506, and 1573??cm?1, which reflects the genetic variations in NPC. Principal component analysis combined with discriminant function analysis for early NPC discrimination yielded a diagnostic accuracy of 86.8%, 92.3%, and 87.9% for early NPC, advanced NPC, and normal nasopharyngeal tissue DNA, respectively. In this exploratory study, we demonstrated the potential of SERS for early detection of NPC based on the DNA molecular study of biopsy tissues.
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