Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar, 608002, Tamilnadu, India.
Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar, 608002, Tamilnadu, India.
J Nutr Biochem. 2019 Jan;63:62-71. doi: 10.1016/j.jnutbio.2018.09.022. Epub 2018 Oct 12.
In this study, the modulatory effect of ferulic acid on P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) was examined in KB Ch8-5 resistant cells and drug-resistant tumor xenografts. We observed that ferulic acid enhanced the cytotoxicity of doxorubicin and vincristine in the P-gp overexpressing KB Ch8-5 cells. Further, ferulic acid enhances the doxorubicin induced γH2AX foci formation and synergistically augmented doxorubicin-induced apoptotic signaling in the drug-resistant cells. It has also been noticed that NF-κB nuclear translocation was suppressed by ferulic acid and that this response might be associated with the modulation of phosphatidyinositol 3-kinase (PI3K)/Akt/signaling pathway. We also found that ferulic acid and doxorubicin combination reduced the size of KB Ch8-5 tumor xenograft by threefold as compared to doxorubicin-alone treated group. Thus, ferulic acid contributes to the reversal of the MDR through suppression of P-gp expression via the inhibition of PI3K/Akt/NF-κB signaling pathway.
在这项研究中，研究了阿魏酸对 P-糖蛋白（P-gp）介导的多药耐药（MDR）的调节作用，在 KB Ch8-5 耐药细胞和耐药肿瘤异种移植中进行了研究。我们观察到阿魏酸增强了 P-gp 过表达的 KB Ch8-5 细胞中多柔比星和长春新碱的细胞毒性。此外，阿魏酸增强了多柔比星诱导的 γH2AX 焦点形成，并在耐药细胞中协同增强了多柔比星诱导的凋亡信号。还注意到阿魏酸抑制了 NF-κB 核易位，这种反应可能与磷脂酰肌醇 3-激酶（PI3K）/Akt/信号通路的调节有关。我们还发现，与单独用多柔比星处理的组相比，阿魏酸和多柔比星联合使用将 KB Ch8-5 肿瘤异种移植的大小减少了三倍。因此，阿魏酸通过抑制 PI3K/Akt/NF-κB 信号通路抑制 P-gp 表达，有助于逆转 MDR。
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