Janus Seth C, Weurtz Beverly, Ondrey Frank G
Department of Otolaryngology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Laryngoscope. 2007 Aug;117(8):1381-8. doi: 10.1097/MLG.0b013e3180679e59.
OBJECTIVES/HYPOTHESIS: Nuclear factor (NF)-kappaB is an early response gene that has been associated with head and neck squamous cell cancer (HNSCC) progression. NF-kappaB activation is induced by some chemotherapy agents, including paclitaxel. The activation of this gene can be correlated with apoptosis resistance. Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate. NF-kappaB levels were evaluated in oral cavity HNSCC lines after treatment with paclitaxel and IP6, alone and in combination. Resulting levels of cell death and apoptosis were assessed, and conclusions are drawn regarding a possible synergistic relationship between paclitaxel and IP6.
NF-kappaB activation in cancer cells treated with paclitaxel and IP6, alone and in combination, was measured by transient transfection, and results were interpreted by luminometry. Cell proliferation of treated cells was measured by MTT assay. Cell viability and apoptosis of cancer cells treated with paclitaxel and IP6 combinations were quantitated by trypan blue staining and Caspase-Glo 3/7 assay, respectively.
IP6 was observed to significantly downregulate NF-kappaB activation in both NA and CA-9-22 oral cavity HNSCC cell lines. Paclitaxel treatments caused increased NF-kappaB activation in the same cell lines. IP6 was observed to mitigate paclitaxel-induced NF-kappaB activation in the CA-9-22 cell line. IP6, when combined with paclitaxel, reduces CA-9-22 cell proliferation, increases cell death, and increases apoptosis, when compared with treatment with paclitaxel alone.
IP6 reduces paclitaxel induced NF-kappaB activation and increases paclitaxel-mediated cell killing and apoptosis. As a well-tolerated and safe supplement, IP6 deserves further study in the treatment of oral cavity squamous cell carcinoma.
目的/假设：核因子（NF）-κB是一种早期反应基因，与头颈部鳞状细胞癌（HNSCC）进展相关。NF-κB的激活由包括紫杉醇在内的一些化疗药物诱导。该基因的激活可能与凋亡抗性相关。肌醇六磷酸（IP6）是一种天然存在的多磷酸化碳水化合物。在用紫杉醇和IP6单独及联合处理口腔HNSCC细胞系后，评估NF-κB水平。评估由此产生的细胞死亡和凋亡水平，并就紫杉醇和IP6之间可能的协同关系得出结论。
通过瞬时转染测量单独及联合使用紫杉醇和IP6处理的癌细胞中NF-κB的激活情况，并通过发光测定法解释结果。通过MTT法测量处理细胞的增殖情况。分别通过台盼蓝染色和Caspase-Glo 3/7测定法定量单独及联合使用紫杉醇和IP6处理的癌细胞的活力和凋亡情况。
观察到IP6可显著下调NA和CA-9-22口腔HNSCC细胞系中NF-κB的激活。紫杉醇处理导致相同细胞系中NF-κB激活增加。观察到IP6可减轻CA-9-22细胞系中紫杉醇诱导的NF-κB激活。与单独使用紫杉醇处理相比，IP6与紫杉醇联合使用时可降低CA-9-22细胞增殖、增加细胞死亡并增加凋亡。
IP6可降低紫杉醇诱导的NF-κB激活，并增加紫杉醇介导的细胞杀伤和凋亡。作为一种耐受性良好且安全的补充剂，IP6在口腔鳞状细胞癌治疗中值得进一步研究。
