Effects of diallyl trisulfide on osteosarcoma acquired drug-resistant cell line and its possible mechanism

LI Ji; CAI Jinfang; ZOU Lin; LI Zongyu

doi:10.3969/j.issn.1002-266X.2018.01.007

Abstract：Objective To observe the effects of diallyl trisulfide ( DATS) on the osteosarcoma acquired drug-resist-ance cell line , and to investigate its possible mechanism .Methods We established an osteosarcoma cell line Saos-2/DOX which acquired drug-resistance to doxorubicin ( DOX) in vitro by the pulse selection .MTT assay was applied to de-termine the half maximal inhibitory concentration (IC50) of Doxorubicin (DOX) on the Saos-2 and Saos-2/DOX cells, be-sides the resistance index (RI) of Saos-2/DOX was calculated.Moreover, the DATS concentration treating Saos-2/DOX without cytotoxicity was selected by MTT assay .The cell viability was detected by MTT assay at 24, 48, and 72 h after the treatment of DOX alone or in combination with DATS on the Saos-2/DOX cells.At 48 h after the treatment of DATS (0, 10, 50, and 100 μmol/L) on the Saos-2/DOX cells, the protein expression levels of pERK 1/2, ERK1/2, pAKT1, and AKT1 were detected by Western blotting .Results The DOX-resistant osteosarcoma cell line Saos-2/DOX was successfully established and the RI of Saos-2/DOX was 6.94.The DATS concentration treating Saos-2/DOX cells without cytotoxicity was 10 μmol/L.The survival rate of Saos-2/DOX-resistant cells treated with DOX 100 μg/L and DATS 10 μmol/L for 24 h was significantly lower than that of DOXS 10μmol/L or DOX 100μg/L, and decreased over the treatment time ( all P<0.05).At 48 h after treatment of different concentrations of DATS , the protein expression level of pERK1/2 was signifi-cantly up-regulated, which was concentration dependent (P<0.05).However, no significant difference was found in the protein expression levels of ERK1/2, pAKT1, and AKT1 (all P>0.05).Conclusion DATS could reverse the acquired drug-resistance of Saos-2/DOX cells by activating the ERK 1/2 signal pathway .