Anti-angiogenesis Effect Of Clarithromycin On Tumor

Cancer is bigger killer in whole world, the burden of this disease is much more important than other diseases in populations .with a long life expectancy. The impact on and cost to society are staggering. Nowadays, there has been an explosion in our understanding of the biology and molecular biology of cancer. This understanding has enabled the development of new strategies for the treatment and chemoprevention. But, because of the lack of efficient diagnostic tools for early detection and of efficient treatment for advanced disease, the prognosis of cancer is generally poor, with a few 5 years survival after diagnosis. The major cause of death from the most common type of cancer is attributable to metastasis.Tumor tissue is highly vascularized. In recent decades, this observation has led to the realization that blood vessels are essential for tumor growth, invasion, and metastasis. Indeed, developing solid primary tumors are thought to remain clinically insignificant, with maximum sizes no greater than about 2 mm, unless they can arrange to steal nourishment from their host. Science Dr. Judah Folkman proposed that tumor neovascularization might be a novel target of cancer therapy almost three decades ago, angiogenesis as a specific target for antitumor therapy has attracted a considerable and increasing general interest in the scientific community. More and more scientists have been studying natural and synthetic angiogenesis inhibitors, also called anti-angiogenesis agents, in the hope that these chemicals will prevent the growth of cancer by blocking the formation of new blood vessels.Angiogenesis means the formation of new blood vessels. It is known to be a complex process that requires endothelial cell proliferation, migration and differentiation into tube-like structures and controlled by extensive interactions between a various peptides and other modulating factors produced by host or tumor cell. Recently, 14-membered ring macrolides antibiotic, including clarithromycin (CAM), erythromycin (EM), and roxithromycin (RXM), have been reported to modulate immune response in a variety of settings and may act as anti-inflammatory agents or biological response modifiers, rather than antibacterial. Some compelling evidence shown they can modulate production of cytokines involved angiogenesis and are potent inhibitor of tumor-induced angiogenesis. Thus, we carry out a series study to confirm the Anti-angiogenesis effect ofclarithromycin in vivo and in vitro. On the other hand, To find angiogenesis inhibitors in clinical practice drugs is an advantageous strategy with low-cost and short-periodicity, the results of these studies can be used in clinical directly.The main results and conclusion showed as below:1 .Clarithromycin inhibited blood vessel formation in chicken chorioallantoiin membrane, with the lowest dose of 30 mmol/L. This anti-angiogenic effect was proportional to the dose of clarithromycin.2.In Matrigel implant assay, Clarithromycin can reduce hemoglobin content and micro-vascular area in Matrigel implant at dosage of 40 mg/kg/day.3.In rat aorta ring explant assay. Clarithromycin at concentration of over 60 mmol/L significantly inhibited generating branch microvessels. The inhibitory effect related to clarithromycin dosage.4.With immunohistochemistry and image analysis, The expression of MMP-9 was declined at protein level in SCLC cells after treated with 30mmol/L clarithromycin for 48 hours, when treated with 40 mmol/L clarithromycin, expression of VEGF was decreased too. A dose-response relationship can be demonstrated in expression of MMP-9 and clarithromycin concentration.5.When human umbilical vein endothelial cell and human small cell lung cancer cell were coculrured in Marigel invasion chamber system, Clarithromycin at concentration of over 30mmol/L significantly inhibited the chemoactic migration of endothelial cell induced by cancer cell in a dose-dependent manner.6.In Lewis Lung Carcinoma-bearing C57BL/6 mice, Clarithromycin effective increased the mean surviva...