Abstract. Marsdenia tenacissima (MT), a traditional Chinese medicine, has been utilized in the treatment of a variety of malignant conditions for decades, but the underlying mechanism remains unclear. Angiogenesis, new blood vessel formation by nearby endothelial cells (ECs) from pre-existing vessels, plays a key role in cancer growth. In the present study, the effects of MT extract (MTE) on EC proliferation and apoptosis in vitro, and on A20 mouse lymphoma growth and angiogenesis in vivo were investigated. MTE exhibited an anti-proliferative effect on the ECs, with a half maximal inhibitory concentration of 11.91±0.24 µl/ml. Acridine orange/propidium iodide staining indicated that cell apoptosis increased with MTE concentration. Flow cytometry revealed that the EC apoptosis rates induced by 0, 6.25, 12.5 and 25 µl/ml MTE were 4.8, 23.3, 49.8 and 92.3%, respectively. In vivo, the volume and weight of the A20 solid tumors were significantly inhibited following administration of 300 µl MTE per day for 14 days (P<0.05). MTE showed extended survivability and a satisfactory security. Subsequent to treatment with MTE, peritumorous angiogenesis was significantly reduced, with lower microvessel density (P<0.05) was quantified by hemotoxylin and eosin staining. Moreover, serum vascular endothelial growth factor, matrix metalloproteinase (MMP)-2 and MMP-9 expression at the protein level in the MTE-treated group, quantified using an ELISA, was significantly lower than that of the control (P<0.05). In a chick chorioallantoic membrane assay, 12.5 and 25 µl/ml MTE distinctly decreased the level of angiogenesis (P<0.05). In conclusion, MTE exhibited potent anti-lymphoma efficacy in vitro and this may be associated with its effects against tumor angiogenesis.
IntroductionAngiogenesis, the process of the formation of new blood vessels from pre-existing ones, plays a key role in the progression of solid tumors and hematological malignancies, such as lymphoma (1). Anti-angiogenesis can inhibit tumor growth and metastasis, and has become an appealing strategy for tumor therapy.Traditional Chinese medicine (TCM) has been used for several thousand years, and has been suggested to aid the prevention and treatment of diseases such as cancer. Over the past 40 years, a number of TCM herbs have become a focus of interest globally; anticancer components have been isolated from medicinal herbs, which have been demonstrated to serve as modifiers of biological responses and as inhibitors of angiogenesis (2).The stem of Marsdenia tenacissima (MT), also known as Marsdeniae tenacissimae (Roxb) Wight et Arn (family Asclepiadaceae), is well known as 'Tong-guan-teng' in TCM. Over the past 30 years, the antitumor effects of MT have aroused attention and passion from researchers. Previous studies have indicated that MT could inhibit proliferation and induce apoptosis in various cancer cell lines, such as HepG2/Dox, SGC 7901, Lewis lung carcinoma, U937, HL60, Jurkat, Raji and RPMI8226 (3-7). Studies in vitro revealed that MT exerts antitumor activity ...