Abstract. Human MOF (males absent on the first), as a histone acetyltransferase, is responsible for histone H4K16 acetylation in human cells. Recent studies have shown that the abnormal gene expression of hMOF is involved in certain primary cancers. Here, we first report the involvement of hMOF expression in clinically diagnosed primary colorectal carcinoma (CRC) and gastric cancer. Simultaneously, the correlation of hMOF expression and clinicopathological features in CRC, gastric cancer and renal cell carcinoma (RCC) was analyzed. The hMOF mRNA expression was assessed in 44 CRC, 16 gastric cancer and 47 RCC human tissue samples by quantitative PCR (qPCR). Statistical analysis of qPCR data revealed a significant reduction (>2-fold decrease) of hMOF gene expression in CRC, 57% (25/44), 94% (15/16) in gastric cancer and 74% (35/47) in RCC tissues of the patients. In patients with CRC, lymph node metastasis and tumor stage were associated with hMOF expression patterns. However, no significant association between hMOF expression and tumor types emerged (p>0.05). Interestingly, in patients with gastric cancer, although no statistically significant difference was found between adjacent (<2 cm away from the cancer tissue) and normal tissues (>5 cm away from the cancer tissue), >2-fold reduction of hMOF expression in adjacent tissues had already appeared in 35% of patients. In addition, low expression of hMOF was strongly correlated with tumor differentiation (p<0.05) and survival of patients with gastric cancer (p<0.001). While in patients with RCC, downregulation of hMOF was connected to ccRCC and tissues with T1 tumor status. Our results suggest that downregulation of hMOF may be common in cancer tissues, and may represent a novel biomarker for tumor diagnosis.
Background:
Photodynamic therapy (PDT) is widely recognized as a promising way to cure cancer. However, the limited tumor homing property of currently available drug delivery systems (DDSs) is the bottleneck for the delivery of photodynamic agents.
Purpose:
In our study, we decorated silica nanoparticles (SLN) with cell membrane (CM) derived from SGC7901 cells to construct carrier (CM/SLN) which was able to to specifically target the homogenous SGC7901 cells.
Materials and methods:
Furthermore, the decent drug loading capability of CM/SLN was adopted to load photodynamic agent chlorins e6 (Ce6) to finally construct aDDS suitable for tumor-targeted PDT of gastric cancer.
Results:
The experimental results suggested that CM/SLN/Ce6 was nano-sized particles with good dispersion and stability in physiological conditions. Moreover, due to the modification of CM,CM/SLN/Ce6 could specifically target the homogenous SGC7901 cells both in vitro and in vivo. Most importantly, further in vivo results demonstrated that the CM/SLN/Ce6 showed a better anticancer outcome compared to SLN/Ce6.
Conclusion:
CM/SLN/Ce6 might be a promising platform for effective tumor targeted PDT of gastric cancer.
Capsaicin (CAP) is the major pungent component of chili pepper and is being evaluated for use against numerous types of tumors. Although CAP is indicated to target multiple signaling pathways, exact mechanisms of how it disturb cancer cell metablism remain obscure. Recent studies revealed Sirtuin 1 (SIRT1) serves as a potential target of CAP in cancer cells, indicating a direct regulation of cancer cell histone acetylation by capsaicin. The present study evaluated the effect of CAP on gastric cancer (GC) cell lines to understand the mechanism of cell growth inhibition. The results showed that CAP could significantly suppress cell growth, while altering histone acetylation in GC cell lines. Further studies found that hMOF, a major histone acetyltranferase for H4K16, is central to CAP-induced epigenetic changes. Reduced hMOF activity was detected in GC tissues, which could be restored by CAP both in vivo and in vitro. These findings revealed an important role of hMOF-mediated histone acetylation in CAP-directed anti-cancer processes, and suggested CAP as a potential drug for use in gastric cancer prevention and therapy.
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