大黄素抗肿瘤分子机制的研究进展

大黄素(emodin,1,3,8-trihydroxy-6-methylanthraquinone),化学名为1,3,8-三羟基-6-甲基蒽醌,属于天然蒽醌类衍生物,是许多中药如大黄、虎杖、何首乌的主要有效成分.研究表明[1],大黄素具有多种药理学作用,如抑制胰酶活性、抗炎、抑菌、抗氧化、利尿、免疫调节、保护肝肾、松弛血管、促进胃肠蠕动及抑制血小板聚集、改善微循环等.

Objective: To study the vaccine potency of gene-modified tumor cells. Methods: The EL-4 lymphoma was transduced with recombinant retrovirus containing the murine GM-CSF gene or B7-1 gene. The effect of gene transduction on antitumor immunity was investigated. Results: Flow cytometry analysis showed that expression of their surface marker between wild-type EL-4 cells and gene transduced tumor cells was the same except for CD80 positive in B7-1 gene transduced cells. GM-CSF gene or B7-1 gene transduced EL-4 cells resulted in remarkable loss of tumorigenicity in syngenetic mice. The systemic protective immunity was induced against the challenge with EL-4/wt cells. Therapeutic vaccine with EL-4/GM-CSF or EL/7-1 cells could retard the growth of established early-stage EL-4/wt tumor significantly, but not retard the growth of late-stage EL-4/wt tumor. Irradiated GM-CSF gene transduced EL-4 cells showed strong vaccine effect against EL-4 cell challenge, but irradiated B7-1 gene transduced EL-4 cells showed weak vaccine effect. Remarkable cooperative antitumor effect against EL-4 cell challenge was observed when both irradiated EL-4/GM-CSF and EL-4/B7-1 were inoculated together. Conclusion: GM-CSF gene or B7-1 gene transduced combination of the two kinds of vaccine may have potential application value in human cancer treatment.

骨转移瘤系统性分子靶向治疗靶点与药理学制剂研究

骨转移瘤骨骼微环境中，肿瘤细胞分泌多种细胞因子促进溶骨活性，而溶骨后释放的储存于骨内的生长因子又促进肿瘤细胞生长与侵袭，从而形成骨质破坏“恶性循环”。虽然骨骼微环境可造成骨质破坏的“恶性循环”，但也为骨转移瘤治疗提供了许多潜在性靶点。骨转移瘤分子靶点以核因子?κB受体活化因子（receptor activator of nuclear factor?κB, RANK）-核因子?κB受体活化因子配体（RANK ligand, RANKL）-骨保护素（osteoprotegerin, OPG）系统研究得为广泛与深入。骨转移瘤细胞可以促进骨基质细胞表达RANKL并抑制OPG的表达，RANKL与OPG比例失调是诱发骨质破坏的重要因素。溶骨产生的转移生长因子β在介导“恶性循环”中的作用越来越突出，转移生长因子β可以促进肿瘤细胞发生上皮-间质转变、血管生成以及免疫抑制。Src家族激酶、内皮素A受体、基质金属蛋白酶以及组蛋白酶K等均为骨转移瘤治疗的潜在性靶点。以狄诺塞麦为代表的靶向药理学制剂的本质均为阻断骨转移瘤骨质破坏“恶性循环”。骨转移瘤靶向制剂除了可以抑制骨转移瘤细胞骨质破坏外，部分还可以产生直接抗原发肿瘤效应，它们在延迟骨相关事件发生、延长患者生存期以及终提高患者生存质量方面发挥着重要作用。骨转移瘤患者已经可以从系统性分子靶向治疗中受益，进一步研发系统性靶向制剂对改善患者治疗选择、增强疗效具有重要意义。