Acta Academiae Medicinae Sinica

Acta Academiae Medicinae Sinica

Acta Academiae Medicinae Sinica ›› 2015, Vol. 37 ›› Issue (2): 215-220.doi: 10.3881/j.issn.1000-503X.2015.02.013

• Orginal Article • Previous Articles     Next Articles

Effects of Melatonin Combined with Cis-platinum or Methotrexate on the Proliferation of Osteosarcoma Cell Line SaOS-2

Ya-peng WANG, Zhi-ping YANG()   

  1. Department of Osteology,Qilu Hospital of Shandong University,Jinan 250012,China
  • Received:2014-09-12 Online:2015-02-28 Published:2015-05-01

Abstract: ObjectiveTo evaluate the effects of melatonin(Mel)combined with cis-platinum(DDP)or methotrexate(MTX)on the proliferation of osteosarcoma cell line SaOS-2,and to explore whether Mel combined with DDP or MTX could play a synergistic antitumor effect.MethodsSaOS-2 was treated with Mel alone or Mel combined with DDP or MTX.Cell counting kit-8 assay was used to measure the cell activities.Combination index(CI)value was used to evaluate the combined effects:CI<1 indicating synergetic effect,CI=1 additive,and CI>1 antagonistic.Flow cytometry was used to analyze cell cycle distribution and cell apoptosis.ResultsAfter treated with Mel(0.5,1,2,4,5 mmol/L),DDP(6.67,16.67,33.33,66.66 μmol/L)or MTX(0.1,0.5,1,2,4 mmol/L)alone,SaOS-2 cell activities decreased in a dose-dependent manner(all P<0.05).The activities of SaOS-2 cell treated with both Mel(1 mmol/L)and DDP or MTX were significantly lower than that of DDP or MTX alone(all P<0.05).CI values of cells exposed to 1 mmol/L Mel plus 6.67,16.67,33.33,and 66.66 μmol/L DDP were 1.18,1.21,1.09,and 0.84,respectively,and CI values of cells exposed to 1 mmol/L Mel plus 0.1,0.5,1,2,and 4 mmol/L MTX were 0.88,0.88,0.83,0.78,and 0.81,respectively.The G1-stage cells were increased and the S-stage cells were reduced when the cells were treated with Mel(1 mmol/L)alone or combined with MTX(0.5 mmol/L)(P<0.05).The S-stage cells were increased when the cells treated with MTX(0.5 mmol/L)(P<0.05).The apoptotic cells were increased when they treated with Mel(1 mmol/L)alone or combined with DDP(16.67 μmol/L)or MTX(0.5 mmol/L)(P<0.05).When the cells were treated with Mel combined with DDP or MTX,the apoptotic cells were more than that of DDP or Mel alone(P<0.05).ConclusionsMel can inhibit SaOS-2 cells activity,block the cell cycle at G1-stage,and induce apoptosis.Mel has an antagonistic effect with lower concentration of DDP but a synergistic effect with MTX or higher concentration of DDP.

Key words: osteosarcoma, melatonin, cis-platinum, methotrexate

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