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Anticancer drug screening test with LDH in nude mouse bearing bone and soft part sarcoma
Abstract:
With the use of human LDH as a marker, growth and remission of four human osteosarcomas (KOS-1, KOS-2, KOS-3, OST) and a malignant fibrous histiocytoma (KMF) transplanted into nude mice were monitored during chemotherapies (Adriamycin [doxorubicin], cisplatin, mitomycin C, cyclophosphamide and vincristine). Four osteosarcomas were effectively treated with Adriamycin and cisplatin, and KMF was treated with Adriamycin, cisplatin, and mitomycin C. Changes in human LDH levels paralleled changes in tumor size and these could be used to predict the death of the animals due to tumor (P less than 0.01). Furthermore, the enzyme increased transiently after administration of the effective drugs.
Insights
Human lactate dehydrogenase (LDH) levels effectively monitored osteosarcoma and malignant fibrous histiocytoma tumor progression in mice during chemotherapy. Elevated LDH indicated tumor growth and predicted animal survival, showing transient increases after effective drug treatments.
Area of Science:
- Oncology
- Biochemistry
- Pharmacology
Background:
- Human osteosarcomas and malignant fibrous histiocytoma are aggressive tumors.
- Chemotherapy is a primary treatment modality for these cancers.
- Biomarkers are needed to monitor treatment efficacy and predict outcomes.
Purpose of the Study:
- To evaluate human lactate dehydrogenase (LDH) as a biomarker for monitoring tumor growth and remission.
- To assess the effectiveness of various chemotherapeutic agents against human osteosarcomas and malignant fibrous histiocytoma xenografts.
- To determine if LDH levels can predict animal survival during chemotherapy.
Main Methods:
- Human osteosarcoma (KOS-1, KOS-2, KOS-3, OST) and malignant fibrous histiocytoma (KMF) cell lines were xenotransplanted into nude mice.
- Tumor-bearing mice were treated with Adriamycin (doxorubicin), cisplatin, mitomycin C, cyclophosphamide, and vincristine.
- Tumor size and serum human LDH levels were monitored throughout the chemotherapy regimens.
Main Results:
- Adriamycin and cisplatin effectively treated four osteosarcomas.
- Adriamycin, cisplatin, and mitomycin C were effective against malignant fibrous histiocytoma.
- Changes in human LDH levels closely correlated with tumor size changes (P < 0.01).
- Transient increases in LDH were observed after administration of effective chemotherapeutic drugs.
- LDH levels predicted animal death due to tumor burden.
Conclusions:
- Human lactate dehydrogenase (LDH) is a reliable biomarker for monitoring the response of osteosarcomas and malignant fibrous histiocytoma to chemotherapy.
- LDH levels can be used to predict tumor progression and animal survival in xenograft models.
- The transient increase in LDH after effective drug administration may indicate drug-induced tumor cell death.