| Summary: | 碩士 === 國立成功大學 === 藥理學研究所 === 98 === Chronic inflammation can result in the formation of cancer. However, the details remain unclear. In our previous study, we demonstrated that CCAAT/enhancer binding protein delta (CEBPD, C/EBPδ, NF-IL6β), a potential tumor suppressor, can respond to the inflammatory factors treatment, and induce apoptosis to inhibit tumor progression. The E2F1-mediated activation of SUZ12/EZH2 can specifically result in inactivation of CEBPD gene through the hypermethylation of promoter to benefit the further process of tumorigenesis. Single compound of anticancer drug easily results in drug-resistant effects. Therefore, a combination treatment could provide an efficient methodology for cancer therapy. Herein, we demonstrated that CEBPD is a common anticancer drug-responsive protein. A structurally related β-diketone compound, hydroxymethyldibenzoylmethane (HMDB), could act through the activation of p38 kinase pathway to activate CEBPD transcription, followed by activation of PPARG2 and GADD153 transcription. Moreover, combination of HMDB and 5-aza-2’-deoxycytidine (5azadC), a DNA methyltransferase inhibitor, showed a synergistic effect on inducing CEBPD expression and cell apoptosis. In addition, in vivo study showed that combination treatment with HMDB and 5azadC can efficiently attenuate the growth of A431 and Huh7 xenografts in SCID mice. Taken together, these results not only provide new insight for the importance of reversing CEBPD induction to serve as therapeutic anticancer targets but also suggest that HMDB combined with 5azadC may provide a better therapeutic way in treatment of cancer patients with lower toxicity.
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