Source: Annual Congress 2010 - Pathology of lung cancer

Abstract

Background. Numerous clinical data suggest that heparin treatment improves survival in cancer patients. The mechanisms for this effect are not fully understood.
Aim.To investigate whether the low molecular weight heparin (LMWH), nadroparin, directly affects lung cancer cell growth.
Materials and methods. Two lung cancer cell lines, A549 and Calu-1, were cultured with nadroparin (5-40 anti-Xa U/ml) for 0, 24, 48, and 72h. In some experiments, dalteparin was used instead of nadroparin. Cell viability was assessed by MTT assay and a trypan blue dye exclusion assay; cell proliferation was measured by bromodeoxyuridine incorporation. Apoptosis was assessed by flow cytometry using annexin V and propidium iodide (PI) binding. Cell cycle distribution was analyzed by flow cytometry using PI staining; cyclin B1 expression was detected by Western blotting.
Results. Nadroparin induced a dose- and time-dependent, significant decrease in cell proliferation in both cell lines (p<0.05). The effect was not due to a pro-apoptotic mechanism. Nadroparin at 40 anti-Xa U/ml for 48h produced obvious changes in the distribution of cell cycle and increased the number of cells in G₂/M phase (control: G0/G1 60.7%±1.6%, S 13.4%±1.9%, G2/M 25.9%±1.9% and nadroparin: G0/G1 47.7%±3.6%, S 18.4%±2.1%, G2/M 33.9%±1.5%). Nadroparin lowered the expression of cyclin B1 after 48h exposure. In contrast, dalteparin did not alter cyclin B1 expression.
Conclusions. Nadroparin inhibits the proliferation of A549 cell line by inducing a G₂/M phase cell-cycle arrest through reduction of cyclin B1 expression. The effect is not a class effect, in that Dalteparin does not alter cyclin B1 expression.

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Y. Carmazzi, M. Iorio, F. Raggi, S. Cianchetti, T. Neri, C. Cordazzo, R. Vanacore, F. Bogazzi, P. Paggiaro, A. Celi (Pisa, Italy). Nadroparin inhibits A549 human adenocarcinoma cell proliferation through down-regulation of cyclin B1 and G2/M phase cell-cycle arrest. Eur Respir J 2010; 36: Suppl. 54, 3258

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