Compound Taxus exerts marked anti-tumor activity and radiosensitization effect on hepatocellular carcinoma cells

Abstract

BackgroundCompound 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. PurposeTo investigate the antitumor activity and radiosensitization effect of Compound Taxus on HCC cells and to preliminarily explore the possible molecule mechanisms involved. MethodsCell 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. ResultsCompound 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. ConclusionOur 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.