Researchers in Shanghai, China, have found a new combination therapy to be effective against tumor cell lines of malignant mesothelioma and non-small cell lung cancer (NSCLC), and suggest the therapy may become a new treatment regimen for these difficult cancers.
Investigators analyzed the combination of onconase (Onc) and an artemisinin (Art) derivative called dihydroartemisinin (DHA), both in vitro and in vivo, and found synergistic effects of Onc plus DHA in suppressing growth and angiogenesis (the creation of new blood vessels) in both NSCLC and malignant mesothelioma cells.
Their results, published on Sept. 2 in Acta Biochimica et Biophysica Sinica, were in a study titled “Combination of onconase and dihydroartemisinin synergistically suppresses growth and angiogenesis of non–small-cell lung carcinoma and malignant mesothelioma.”
Similar to the synergistic effects seen in NSCLC and malignant mesothelioma cell lines, in vivo experiments showed that the antitumor effect of Onc was notably enhanced by DHA in mouse models. In fact, the researchers found that the combination therapy was more effective in reducing tumor growth than either treatment (Onc or DHA) administered to separate groups of mice as monotherapy. Importantly, no adverse effects were reported after the combination treatment.
Results of the matrigel plug test, a method of evaluating an organism’s ability to create new blood vessels, demonstrated that the Onc/DHA combination markedly suppressed angiogenesis in mice. This implies that the anti-angiogenesis effects may contribute significantly to the in vivo antitumor effects of the combination treatment, and the combination may have the potential to become a novel treatment regimen for NSCLC and mesothelioma, according to the scientists.
The researchers concluded that their findings suggest complete suppression of tumor growth in the Onc/DHA combination treatment animal group, while only moderate suppression was achieved in mice treated with either drug as monotherapy. The team strongly believes that DHA can indeed enhance Onc’s anti-angiogenesis activity.
Their work might lead to the development of a new therapeutic regimen with much less toxicity than currently available treatments for malignant mesothelioma, resulting in fewer side effects.
Researchers also believe that this combination may also have potential applications in tumor-preventive treatments, such as metronomic chemotherapy (a kind of therapy based on suppressing tumor angiogenesis). Metronomic chemotherapy shifts the main treatment target from eliminating tumor cells to suppressing tumor angiogenesis, to stop tumor progression and shift tumors into a dormant state. This approach involves a lower dose of the chemo drug, and eliminates the need for long drug-free periods due to its low toxicity and proven potent anti-angiogenesis activity.