title: Rigosertib is a more effective radiosensitizer than cisplatin in concurrent chemoradiation treatment of cervical carcinoma, in vitro and in vivo.
abstract: OBJECTIVE
  To compare rigosertib versus cisplatin as an effective radiosensitizing agent for cervical malignancies.
  
  
  METHODS
  Rigosertib and cisplatin were tested in cervical cancer cell lines, HeLa and C33A. A 24-hour incubation with rigosertib and cisplatin, before irradiation (2-8 Gy), was used for clonogenic survival assays. Cell cycle analysis (propidium iodide staining) and DNA damage (γ-H2AX expression) were evaluated by fluorescence-activated cell sorter cytometry. Rigosertib was also tested in vivo in tumor growth experiments on cervical cancer xenografts.
  
  
  RESULTS
  Rigosertib was demonstrated to induce a G2/M block in cancer cells. Survival curve comparison revealed a dose modification factor, as index of radiosensitization effect, of 1.1-1.3 for cisplatin and 1.4-2.2 for rigosertib. With 6-Gy irradiation, an increase in DNA damage of 15%-25% was achieved in both HeLa and C33A cells with cisplatin pretreatment, and a 71-108% increase with rigosertib pretreatment. In vivo tumor growth studies demonstrated higher performance of rigosertib when compared with cisplatin, with 53% longer tumor growth delay.
  
  
  CONCLUSIONS
  Rigosertib was more effective than cisplatin when combined with radiation and caused minimal toxicity. These data support the need for clinical trials with rigosertib in combination therapy for patients with cervical carcinoma.
authors: Department of Pathology, Albert Einstein College of Medicine, Bronx, New York.
authors: Lorenzo
authors: L
authors: Agoni
authors: Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York.
authors: Indranil
authors: I
authors: Basu
authors: Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York; Biophysics Research Institute of America, North Miami Beach, Florida.
authors: Seema
authors: S
authors: Gupta
authors: Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York.
authors: Alan
authors: A
authors: Alfieri
authors: Department of Gynecologic Oncology, University of Brescia, Brescia, Italy.
authors: Angela
authors: A
authors: Gambino
authors: Department of Gynecologic Oncology, Albert Einstein College of Medicine, Bronx, New York.
authors: Gary L
authors: GL
authors: Goldberg
authors: Department of Oncological Sciences, Mount Sinai School of Medicine, New York, New York.
authors: E Premkumar
authors: EP
authors: Reddy
authors: Department of Pathology, Albert Einstein College of Medicine, Bronx, New York; Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York. Electronic address: cguha@montefiore.org.
authors: Chandan
authors: C
authors: Guha
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002469:Cell Separation; D002470:Cell Survival; D059248:Chemoradiotherapy / Q000379:methods*; D002945:Cisplatin / Q000627:therapeutic use; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005434:Flow Cytometry; D005998:Glycine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008819:Mice, Nude; D008938:Mitosis / Q000187:drug effects / Q000528:radiation effects; D009368:Neoplasm Transplantation; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D013450:Sulfones / Q000627:therapeutic use*; D013997:Time Factors; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*
chemical_list: D011838:Radiation-Sensitizing Agents; D013450:Sulfones; C507134:ON 01910; D002945:Cisplatin; D005998:Glycine