Sugiyasu Kenjiro, Nanno Katsuhiko, Tamai Noriyuki, Hashimoto Nobuyuki, Kishida Yuki, Yoshikawa Hideki, Myoui Akira
Department of Orthopaedics, Osaka University Graduate School of Medicine, Osaka University Hospital, Suita, Osaka 565-0871, Japan.
Oncol Lett. 2011 May;2(3):407-412. doi: 10.3892/ol.2011.277. Epub 2011 Mar 21.
Nuclear factor (NF)-κB has been shown to be associated with cancer resistance to radiotherapy (RT), and is constitutively active in the murine osteosarcoma cell line, LM8. Parthenolide has been reported to show antitumor activity through inhibition of the NF-κB pathway. In this study, we investigated the radio-sensitizing activity of parthenolide. We established Luc-LM8, a stable transfectant reporter construct of NF-κB transcriptional activity into LM8. Luc-LM8 maintained the malignancy observed with LM8. In vitro, Luc-LM8 cells were cultured with or without parthenolide treatment, irradiated, and subjected to cell viability and apoptosis assays. In vivo, to investigate whether parthenolide enhances radio-sensitivity of tumors, a tumor growth assay was conducted. Parthenolide enhanced the growth inhibitory effect of RT and induced the apoptosis of Luc-LM8 cells with RT in vitro. The in vivo tumor growth was significantly suppressed in the mice treated with parthenolide and RT. The present study suggests that parthenolide sensitizes Luc-LM8 cells to irradiation. Thus, parthenolide is a potential candidate for use as a potent radio-sensitizing drug for use in cancer RT.
核因子（NF）-κB已被证明与癌症对放疗（RT）的抗性有关，并且在小鼠骨肉瘤细胞系LM8中呈组成性激活。据报道，小白菊内酯通过抑制NF-κB途径显示出抗肿瘤活性。在本研究中，我们研究了小白菊内酯的放射增敏活性。我们构建了Luc-LM8，一种将NF-κB转录活性稳定转染到LM8中的报告基因构建体。Luc-LM8保持了与LM8相同的恶性程度。在体外，将Luc-LM8细胞在有或没有小白菊内酯处理的情况下培养，进行照射，并进行细胞活力和凋亡检测。在体内，为了研究小白菊内酯是否增强肿瘤的放射敏感性，进行了肿瘤生长检测。小白菊内酯增强了放疗的生长抑制作用，并在体外诱导了接受放疗的Luc-LM8细胞凋亡。在用小白菊内酯和放疗处理的小鼠中，体内肿瘤生长明显受到抑制。本研究表明，小白菊内酯使Luc-LM8细胞对辐射敏感。因此，小白菊内酯是一种有潜力的候选药物，可作为一种有效的放射增敏药物用于癌症放疗。
