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Role of dalteparin sodium on the growth of cancer cells and tumor-associated angiogenesis in A549 human lung cancer cell line and grafted mouse model


1 Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Bengbu Medical College, Lung Cancer Diagnosis and Treatment Center of Anhui Province, Anhui Provincial Key Laboratory of Clinical Basic Research on Respiratory Disease, Bengbu, China
2 Department of Respiration, Anhui Provincial Hospital, Hefei, China
3 Department of Respiration, The Third People's Hospital of Bengbu, Bengbu, China
4 Department of Respiration, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China

Correspondence Address:
Linian Huang,
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Bengbu Medical College, Lung Cancer Diagnosis and Treatment Center of Anhui Province, Anhui Provincial Key Laboratory of Clinical Basic Research on Respiratory Disease, No. 287 Chang Huai Road, Bengbu 233004
China
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Source of Support: None, Conflict of Interest: None

Purpose: To investigate the effects of dalteparin sodium on the expression of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR), and hypoxia-inducible factor 1α (HIF-1α) in A549 human lung cancer (LC) cell line and a human A549-grafted nude mouse model. Materials and Methods: A549 human lung adenocarcinoma cell line was divided into control group, treated using normal saline (NS); and dalteparin sodium groups, receiving 5, 15, 50, and 150 IU/ml of dalteparin sodium, respectively. Human A549-grafted nude mouse was induced through subcutaneous (SC) injection of A549 (5 × 10 6 /0.2 ml) into the right armpit, and randomly assigned into control group (n = 6) receiving intraperitoneal (i.p.) injection of NS, cisplatin (DDP) group (n = 6, 3 mg/kg DDP alone, i.p., for 3 days), low molecular weight heparin (LMWH) group (n = 6) receiving SC injection of 1500 IU/kg dalteparin sodium for 35 days, and DDP plus LMWH group (n = 6, 3 mg/kg DDP, i.p., for 3 days, followed by SC injection of 1500 IU/kg dalteparin sodium for 35 days). Results: Significant difference was noted in the messenger RNA expression of VEGF, VEGFR, and HIF-1α after treating with heparin with a concentration of 15, 50, or 150 IU/ml in the A549 cell line at 24 and 48 h, respectively. In the human A549-grafted nude mouse model, a significant reduction was noted in the expression of VEGF, VEGFR, and HIF-1α in the tumor mass harvested from the mice receiving administration of dalteparin sodium plus DDP. Conclusion: Dalteparin sodium had the inhibitory effects on the growth of human LC A549 cells in vitro and A549 LC xenograft model, which could be enhanced when administrated together with DDP.


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    -  Wang D
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