Expression of drug resistance related proteins in osteosarcoma and soft tissue sarcoma and its correlations with chemotherapy resistance

AIM: To explore the expression of four kinds of drug resistance related protein: P-glycoprotein (P-gp), glutathione-S-transferases-π (GST-π), lung resistance protein (LRP), multidrug resistance related protein (MRP) in osteosarcoma cell lines Saos2 and U2OS, and in osteosarcoma and soft tissue sarcoma tissues from 34 patients and their correlations with chemotherapy resistance.METHODS: The expression of protein was detected by flow cytometry (FCM).Chemotherapy resistance was analyzed by MTT assay.RESULTS: Expression of drug resistance related protein was lower in Saos2 cell line than that in U2OS cells.Chemotherapy sensitivity on adriamycin (ADM), cisplatinum (DDP), fluorouracilum (5-Fu), mitomycin (MMC), dacarbazine (DTIC), vincristine (VCR) was higher in Saos2 than those in U2OS cells.After the two cell lines were treated respectively with 1/5 50% inhibitory concentration (IC50) doses of ADM and DDP, the expression increasing range of GST-π was 33%-43%.The nonsensitive rate on ADM, DDP, 5-Fu, MMC, DTIC, VCR, methotrexate (MTX) in 34 patients were 41.18％, 17.65％, 47.06％, 50.00％, 76.47％, 61.76％ and 52.94％, respectively.The expression of P-gp, GST-π, LRP, MRP were 1.54, 2.58, 1.91 and 1.86, respectively.The correlation analysis showed that the expression of P-gp had positive correlation with resistance on ADM (r=0.485, P<0.01), the expression of GST-π had correlations with resistance on ADM, DDP, 5-Fu and MMC.The r value was 0.402, 0.458, 0.364 and 0.500,respectively.The corresponding value of P was <0.05, <0.01, <0.05 and <0.01,respectively.The observed expression of resistance related proteins was not significant difference between different gender, different age, different pathological type and different tumor size in osteosarcoma and soft tissue sarcoma patients (P>0.05).The expression of GST-π was increased dramatically in patients receiving chemotherapy preoperatively.The preoperative level of GST-π was higher in recurrent patients by follow-up survey than that in patients without recurrence (P<0.05).CONCLUSIONS: Individual difference was obvious in chemotherapy sensitivity and expression of resistance related proteins in different patients.Chemotherapy induced the upregulation of GST-π expression.Primary high expression of GST-π was the main mechanism of resistance in osteosarcoma and soft tissue sarcoma patients, and related with prognosis.