title: Saikosaponin-d increases the radiosensitivity of smmc-7721 hepatocellular carcinoma cells by adjusting the g0/g1 and g2/m checkpoints of the cell cycle.
abstract: BACKGROUND
  Saikosaponin-d (SSd), a monomer terpenoid purified from the Chinese herbal drug Radix bupleuri, has multiple effects, including anticancer properties. However, the effect of SSd on tumors exposed to radiation is largely unknown. To investigate the radiosensitizing effect of SSd and its possible mechanism, we combined SSd with radiation therapy to treat SMMC-7721 hepatocellular carcinoma cells under oxia and hypoxia.
  
  
  METHODS
  Cell growth, apoptosis, and cell cycle distribution were examined after treatment with SSd alone, radiation alone, and their combinations under oxia and hypoxia. The protein and mRNA levels of p53, Bcl2, and BAX were measured using western blot analysis and RT-PCR, respectively.
  
  
  RESULTS
  Treatment with SSd alone and radiation alone inhibited cell growth and increased apoptosis rate at the concentration used. These effects were enhanced when SSd was combined with radiation. Moreover, SSd potentiated the effects of radiation to induce G0/G1 arrest in SMMC-7721 cells, and reduced the G2/M-phase population under hypoxia. However, under oxia, SSd only potentiated the effects of radiation to induce G0/G1 arrest, but not G2/M-phase arrest. These effects of SSd alone, radiation alone, and their combination, were accompanied by upregulated expression of p53 and BAX and downregulation of Bcl2 expression under oxia and hypoxia.
  
  
  CONCLUSIONS
  SSd potentiates the effects of radiation on SMMC-7721 cells; thus, it is a promising radiosensitizer. The radiosensitizing effect of SSd may contribute to its effect on the G0/G1 and G2/M checkpoints of the cell cycle.
authors.affiliation: Department of Oncology, Second Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an 710004, P,R, China. wangxijing@21cn.com.
authors.forename: Bao-Feng
authors.initials: BF
authors.lastname: Wang
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Dai
authors.forename: Xi-Jing
authors.initials: XJ
authors.lastname: Wang
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Bai
authors.forename: Shuai
authors.initials: S
authors.lastname: Lin
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Ma
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Wang
authors.forename: Ling-Qin
authors.initials: LQ
authors.lastname: Song
authors.forename: Xiu-Long
authors.initials: XL
authors.lastname: Ma
authors.forename: Ying
authors.initials: Y
authors.lastname: Zan
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Min
authors.forename: Yan-An
authors.initials: YA
authors.lastname: Cheng
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D059447:Cell Cycle Checkpoints / Q000187:drug effects* / Q000528:radiation effects; D045744:Cell Line, Tumor; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D012503:Saponins / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D014965:X-Rays; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011838:Radiation-Sensitizing Agents; D012503:Saponins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D009828:Oleanolic Acid; C025759:saikosaponin D