Abstract
BackgroundAberrant expression of heparanase (Hpa) is associated with apoor prognosis in ovarian and cervical cancer patients. Inhibitors of Hpa can prevent the growth and metastasis of malignant tumor cells, and suramin may be such a compound that has strong anti-proliferative effects on several kinds of cancer cells. We have therefore tested whether the growth inhibiting effect of suramin on ovarian and cervical cancer cells is due to downregulation of Hpa expression.ResultsSuramin at 300–600 μg/ml significantly inhibited HO-8910 PM and HeLa cell growth at 24 h, in both a time-dependent and dose-dependent manner, with an IC50 of 320 μg/ml and 475 μg/ml, respectively. Suramin at 300 μg/ml significantly decreased the expression of Hpa mRNA (P < 0.005) and protein (P < 0.005) in both HO-8910 PM and HeLa cells at 48 h.ConclusionsThe inhibitory effect of suramin on Hpa enzyme may be due to downregulating of its expression in cancer cells. These findings confirm the importance of Hpa in tumor growth and the potential clinical application of Hpa inhibitors in the treatment of ovarian and cervical cancer.
Highlights
Aberrant expression of heparanase (Hpa) is associated with apoor prognosis in ovarian and cervical cancer patients
Changes of cell morphology in HO-8910 PM cells and HeLa cells after suramin treatment Changes of cell morphology in HO-8910 PM cells and HeLa cells were explored as part of its dose–response and time–response effects
The IC50 values of HO-8910 PM and HeLa were 319 μg/ml, 476 μg/ml, respectively (Figure 2b).Plasma concentration of ≥350 μg/ml suramin led to a doselimiting neurotoxicity [30]
Summary
Aberrant expression of heparanase (Hpa) is associated with apoor prognosis in ovarian and cervical cancer patients. Inhibitors of Hpa can prevent the growth and metastasis of malignant tumor cells, and suramin may be such a compound that has strong anti-proliferative effects on several kinds of cancer cells. We have tested whether the growth inhibiting effect of suramin on ovarian and cervical cancer cells is due to downregulation of Hpa expression. Due to no effective early detection methods, ~70% ovarian cancers are often diagnosed at advanced stage. With the introduction of new treatment modalities, clinical results have been significantly improved, but the ovarian cancer 5-year survival rate is only 44% [1]. Uterine cervical cancer is another major healthcare concern worldwide, especially in the less developed countries. Systemic chemotherapy or radiochemotherapy remains the standard treatment for those patients, their responses to cytotoxic drugs are not satisfactory, and
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