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[Expression of MDR1 and GST-pi in osteosarcoma and soft tissue sarcoma and their correlation with chemotherapy
Ling Wei1, Xian-Rang Song, Xing-Wu Wang
1Cancer Research Center of Shandong Tumor Hospital, Jinan 250117, China.
Objective:
To explore the expression of multidrug resistance gene 1 ( MDR1), glutathione-S-transferases-pi (GST-pi) in osteosarcoma and soft tissue sarcoma tissues from 34 patients and their correlation with chemotherapy resistance.
Methods:
MDR1 and GST-pi expressions were analyzed by real-time fluorescence quantitative polymerase chain reaction (FQ-PCR) and flow cytometry (FCM) at mRNA and protein levels, respectively. Chemotherapy sensitivity on adriamycin, cisplatinum, fluorouracil, mitomycin C, dacarbazine, vincristine, methotrexate in tumor tissues were detected by MTT assay.
Results:
The nonsensitive rates on adriamycin, cisplatinum, fluorouracil, mitomycin C, dacarbazine, vincristine, methotrexate in tumor tissues were 41.18%, 17.7%, 47.1%, 50.0%, 76.5%, 61.8% and 52.9%, respectively. The expression of P-glycoprotein (P-gp) and GST-pi in tumor tissues was 1.54 and 2.58 (relative fluorescence intensity). Chi2 analysis showed that there was a positive correlation between P-gp expression and drug resistance on ADM, GST-pi expression and resistance on ADM, DDP and MMC (P < 0.05). There was not seen obvious correlation between expression of MDR1, GST-pi and age, gender, pathological type, tumor size in osteosarcoma and soft tissue sarcoma patients (P > 0.05). The expression of GST-pi was increased in patients receiving preoperative chemotherapy. The rate of postoperative recurrence was higher in patients with higher GST-pi expression level than those with lower GST-pi expression level before operation (P < 0.05).
Conclusion:
Individual differences exist in chemotherapy sensitivity and expression of MDR1 and GST-pi in osteosarcoma and soft tissue sarcomas patients. Chemotherapy can induce up-regulation of GST-pi protein expression. Primary high expression of GST-pi is the main mechanism of resistance of osteosarcoma and soft tissue sarcomas to chemotherapy and is related to poor prognosis.
Insights
High expression of glutathione-S-transferases-pi (GST-pi) is linked to chemotherapy resistance and poor prognosis in osteosarcoma and soft tissue sarcoma patients. Chemotherapy can also increase GST-pi levels, impacting treatment outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Osteosarcoma and soft tissue sarcomas exhibit variable responses to chemotherapy.
- Multidrug resistance (MDR) is a significant challenge in treating these cancers.
- Identifying biomarkers for drug resistance is crucial for personalized treatment strategies.
Purpose of the Study:
- To investigate the expression levels of multidrug resistance gene 1 (MDR1) and glutathione-S-transferases-pi (GST-pi) in sarcoma tissues.
- To determine the correlation between MDR1 and GST-pi expression and resistance to common chemotherapeutic agents.
- To assess the impact of chemotherapy on GST-pi expression and its relationship with patient prognosis.
Main Methods:
- Real-time fluorescence quantitative polymerase chain reaction (FQ-PCR) and flow cytometry (FCM) were used to analyze MDR1 and GST-pi mRNA and protein expression.
- The MTT assay was employed to evaluate tumor tissue sensitivity to adriamycin, cisplatinum, fluorouracil, mitomycin C, dacarbazine, vincristine, and methotrexate.
- Statistical analysis (Chi-squared) was performed to identify correlations between gene expression and drug resistance, as well as clinical factors.
Main Results:
- Tumor tissues showed varying degrees of resistance to different chemotherapeutic agents, with high rates for dacarbazine (76.5%) and vincristine (61.8%).
- Elevated expression of P-glycoprotein (P-gp) and GST-pi was observed, with positive correlations found between P-gp and resistance to adriamycin, and GST-pi and resistance to adriamycin, cisplatinum, and mitomycin C.
- Higher GST-pi expression before operation correlated with increased rates of postoperative recurrence, and chemotherapy was found to induce GST-pi upregulation.
Conclusions:
- Significant individual variability exists in chemotherapy sensitivity and the expression of MDR1 and GST-pi in sarcoma patients.
- Primary high expression of GST-pi is a key mechanism contributing to chemotherapy resistance in osteosarcoma and soft tissue sarcomas, indicating a poor prognosis.
- Chemotherapy can induce an increase in GST-pi protein expression, potentially exacerbating drug resistance.
