Therapeutic strategy targeting NFκB-IL6 pathway against progression and paraneoplastic syndrome in prostate cancer

本研究旨在探讨核因子κB-IL 6途径在前列腺癌中的病理生理作用以及包括二羟甲基氧奎诺米星在内的核因子κB抑制剂对前列腺癌的抗肿瘤作用。DHMEQ对前列腺癌细胞有明显的细胞毒作用，呈剂量和时间依赖关系，细胞周期中G2/M期阻滞显著增加，多西紫杉醇对前列腺癌细胞的细胞毒作用增强。DHMEQ可显著增强辐射对前列腺癌的细胞毒作用，其机制可能是通过抑制辐射诱导的NFκB活性升高，提高辐射联合应用对细胞的G2/M期阻滞比例。抑制核因子κB活性可能成为前列腺癌治疗的新途径。

This study was undertaken to elucidate the pathophysiological role of NFκB－IL6 pathway and antitumor effects of NF κB inhibitors including dihydroxymethylepoxyquinomicin (DHMEQ) in prostate cancer. DHMEQ showed significant cytotoxic effects on prostate cancer cells in dose dependent and time dependent manners, produced a significant increase in G2/M arrest in the cell cycle and enhanced the cytotoxic effects of docetaxel on prostatecancer cells. DHMEQ significantly enhanced cytotoxic effects of radiation on prostate cancer, presumably through inhibiting the increased NFκB activity induced by radiation and enhancing the proportion of G2/M arrest in the cells in combination with radiation. Inhibition of NFκB activity may become a new therapeutic modality for treating prostate cancer.