title: Investigation of antitumor effects of sorafenib and lapatinib alone and in combination on MCF-7 breast cancer cells.
abstract: BACKGROUND
  Breast cancer evolution and tumor progression are controlled by complex interactions between steroid receptors and growth factor receptor signaling. Aberrant growth factor receptor signaling can augment or suppress estrogen receptor function in hormone-dependent breast cancer cells. Thus, we aimed to investigate antitumor effects of sorafenib and lapatinib alone and in combination on MCF-7 breast cancer cells.
  
  
  METHODS
  Cytotoxicity of the sorafenib and lapatinib was tested in MCF-7 cells by XTT assays. 50, 25, 12.5 and 6.25μM concentrations of sorafenib and 200, 100, 50 and 25μM concentrations of lapatinib were administered alone and in combination. Results were evaluated as absorbance at 450nM and IC50 values are calculated according to the absorbance data
  
  
  RESULTS
  Both sorafenib and lapatinib showed concentration dependent cytotoxic effects on MCF-7 cells. Sorafenib exerted cytotoxic effects with an IC50 value of 32.0μM; in contrast with lapatinib the IC50 was 136.6μM. When sorafenib and lapatinib combined, lapatinib increased cytotoxic effects of sorafenib at its ineffective concentrations. Also at the concentrations where both drugs had cytotoxic effects, combination show strong anticancer effects and killed approximately 70 percent of breast cancer cells.
  
  
  CONCLUSIONS
  Combinations of tyrosine kinase inhibitors and cytotoxic agents or molecular targeted therapy has been successful for many types of cancer. The present study shows that both sorafenib and lapatinib alone are effective in the treatment of breast cancer. Also a combination of these two agents may be a promising therapeutic option in treatment of breast cancer.
authors.affiliation: Department of Medical Oncology, Cumhuriyet University, Sivas, Turkey E-mail : kacanturgut@gmail.com.
authors.forename: Turgut
authors.initials: T
authors.lastname: Kacan
authors.forename: Ahmet
authors.initials: A
authors.lastname: Altun
authors.forename: Gulsah Gultekin
authors.initials: GG
authors.lastname: Altun
authors.forename: Selen Baloglu
authors.initials: SB
authors.lastname: Kacan
authors.forename: Bulent
authors.initials: B
authors.lastname: Sarac
authors.forename: Mehmet Metin
authors.initials: MM
authors.lastname: Seker
authors.forename: Aykut
authors.initials: A
authors.lastname: Bahceci
authors.forename: Nalan
authors.initials: N
authors.lastname: Babacan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D000077341:Lapatinib; D061986:MCF-7 Cells; D058990:Molecular Targeted Therapy; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D000077157:Sorafenib; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077341:Lapatinib; D009536:Niacinamide; D000077157:Sorafenib; C512478:EGFR protein, human; D066246:ErbB Receptors