Carboxyamidotriazole Dexamethasone Anti-tumor Effect Of Preliminary Exploration

Background:Carboxyamidotriazole (CAI), a non-cytotoxic anticancer drug, newly developed by National Institute of Cancer (NCI) of the United States, has been proven to be tumor-suppressive, anti-angiogenic. Our lab has testified its analgesic and anti-inflammatory effects. Glucocorticoid, commonly used in combination chemotherapy against cancer, has been proven to be anti-inflammatory and anti-angiogenic. Dexamethasone (DEX) is a kind of potent synthetic glucocorticoid. This study aims to observe the tumor-suppressive effects of CAI, DEX and their combination, and to explore the anticancer mechanism.Methods:A mouse model with transplanted tumor was established to evaluate the anti-cancer effects of the CAI, DEX and their combination. Transplanted tumors have been sampled. Some of them were sliced into cryosections and stained with markers of blood vessels immunohistochemically. The anti-angiogenic effects of CAI, DEX and their combination are evaluated on the histological observations. Other tissue samples were homogenized followed by ELISA to detect the level of VEGF, and then determined the inhibitory effects of CAI, DEX and their combination on VEGF level in carciogenic microenvironment.Results:1. CAI did significantly inhibit the growth of mouse transplanted tumor comparing to PEG400solvent control group (p<0.05). While DEX didn’t show significant inhibition comparing to normal saline control group.2. The combination of CAI and DEX showed more significant inhibitory effect on the growth of transplanted tumor than single drug respectively. This effect was additive rather than synergetic.3. CAI highly significantly inhibited angiogenesis within transplanted tumor tissue, comparing to PEG400solvent control group (p<0.01). Also did DEX, comparing to normal saline control group (p<0.01). 4. The combination of CAI and DEX showed more significant anti-angiogenic effect than single drug respectively. This effect was additive rather than synergetic.5. CAI highly significantly downregulated VEGF level within transplanted tumor tissue, comparing to PEG400solvent control group (p<0.01). Also did DEX, comparing to normal saline control group (p<0.01).6. The combination of CAI and DEX showed no significantly statistic difference with either of these two drugs alone, with respect to the inhibitory effect on VEGF level within transplanted tumor tissue.Conclusion:CAI possesses the inhibitory effect on the growth and development of mouse transplanted tumor, as well as anti-angiogenic effect within tumor tissue. These effects can be enhanced by the combination of DEX. The anti-angiogenic effect of CAI may be attributed to its downregulation of VEGF level. However, this downregulatory effect is not enhanced by the addition of DEX, leading to the speculation that the anti-angiogenic effect of CAI may work through other mechanisms as well.