■复方红豆杉胶囊,作为抗肿瘤中成药,作为非小细胞肺癌(NSCLC)和其他一些恶性肿瘤的辅助治疗,但是关于其抗肿瘤活性和对肝细胞癌(HCC)细胞的放射增敏作用的研究很少。
■研究复方红豆杉对肝癌细胞的抗肿瘤活性和放射增敏作用,并初步探讨其可能的分子机制。
■细胞活力,细胞周期分布,凋亡,CCK-8法检测DNA损伤修复和蛋白表达水平,流式细胞术,免疫荧光染色,蛋白质印迹分析和免疫组织化学染色,分别。通过管形成和VM形成测定评估了迁移和侵袭活性以及血管生成拟态(VM)形成和血管生成。辐射存活曲线是从人类HCC细胞系的集落形成测定中获得的,Smmc7721和Bel7402细胞,在接受X射线照射之前,用或不用红豆杉进行预处理。建立Bel7402荷瘤小鼠模型,并通过分析接受不同治疗的不同组的肿瘤体积和肿瘤重量来评价化合物红豆杉在体内的放射增敏作用。
■化合物紫杉降低了活力,诱导G2/M逮捕,促进细胞凋亡,抑制迁移和入侵,并抑制Smmc7721和Bel7402细胞中的VM形成和血管生成。此外,复方红豆杉抑制辐射诱导的DNA损伤修复,增强了Smmc7721和Bel7402细胞的放射敏感性,并提高了Bel7402荷瘤小鼠的放射治疗效果。与单独的化合物红豆杉或单独的辐射相比,与化合物红豆杉组合的放射疗法显示出最佳的肿瘤抑制。此外,复方红豆杉体内外显著下调NF-κBp65、p-NF-κBp65和Bcl-2,上调Bax,然而NF-κBp65过表达逆转了红豆杉对肝癌细胞的促凋亡作用,表明NF-κB信号通路可能是复合紫杉调节生物反应的重要信号介质。
■我们的研究结果表明,复方红豆杉对肝癌细胞具有显著的抗肿瘤活性和显著的放射增敏作用,使复方红豆杉有可能成为HCC管理的一种有前途的辅助方式,并在未来成为HCC的潜在放射增敏剂。
UNASSIGNED: Compound Taxus capsule, as an antineoplastic Chinese patent drug, has been increasingly applied as an adjunctive treatment for the management of non-small-cell lung cancer (NSCLC) and some other malignancies, but research about its antitumor activity and radiosensitization effect on hepatocellular carcinoma (HCC) cells is very rare.
UNASSIGNED: To investigate the antitumor activity and radiosensitization effect of Compound Taxus on HCC cells and to preliminarily explore the possible molecule mechanisms involved.
UNASSIGNED: Cell viability, cell cycle distribution, apoptosis, DNA damage repair and protein expression levels were detected by CCK-8 assay, flow cytometry, immunofluorescence staining, western blotting analysis and immunohistochemical staining, respectively. The migration and invasion activities and vasculogenic mimicry (VM) formation and angiogenesis were evaluated by tube formation and VM formation assay. Radiation survival curves were obtained from the colony formation assay in human HCC cell lines, Smmc7721 and Bel7402 cells, pretreated with or without Compound Taxus before receiving X-ray irradiation. A Bel7402 tumor-bearing mouse model was established and the radiosensitization effect of Compound Taxus in vivo was evaluated by analyzing tumor volume and tumor weight in different groups receiving different treatments.
UNASSIGNED: Compound Taxus decreased viability, induced G2/M arrest, promoted apoptosis, suppressed migration and invasion, and inhibited VM formation and angiogenesis in Smmc7721 and Bel7402 cells. Furthermore, Compound Taxus inhibited irradiation-induced DNA damage repair, enhanced the radiosensitivity of Smmc7721 and Bel7402 cells and improved the anti-tumor therapeutic efficacy of irradiation in Bel7402 tumor-bearing mice. Radiotherapy in combination with Compound Taxus showed the best tumor inhibition compared to that of Compound Taxus alone or irradiation alone. In addition, Compound Taxus significantly down-regulated NF-κB p65, p-NF-κB p65 and Bcl-2, and up-regulated Bax in vitro and in vivo, yet NF-κB p65 overexpression reversed the proapoptotic effect of Taxus on HCC cells, indicating that the NF-κB signaling pathway might be an important signal mediator in the Compound-Taxus-modulated biological responses.
UNASSIGNED: Our findings suggest that Compound Taxus shows marked antitumor activity and significant radiosensitization effect on HCC cells, making it possible for Compound Taxus to become a promising auxiliary modality for HCC management and a potential radiosensitizer of HCC in the future.