Thangapazham Rajesh L, Sharma Anuj, Gaddipati Jaya P, Singh Anoop K, Maheshwari Radha K
Department of Pathology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
J Exp Ther Oncol. 2006;6(1):13-21.
The current therapy for prostate cancer includes radical prostatectomy, radiation therapy and hormonal ablation. Chemotherapy also provides beneficial results for some patients with advanced prostate cancer but with several harmful side effects. Hence there is a need to identify and develop alternate therapies, which can reduce the disease progression with minimal or few side effects. Earlier studies from our laboratory have shown that a Polyherbal mixture, Brahma Rasayna (BR) rich in anti-oxidant principles has a potential to be an anti-tumor agent. BR treatment of MAT-LyLu cell inoculated Copenhagen rats resulted in a decrease of palpable tumor incidence, delay in tumor occurrence and lower mean tumor volumes. Also, a significant reduction in tumor weight and lung metastasis was observed in BR treated animals in comparison to untreated controls. In the present study, we focused to examine the effect of BR on angiogenesis and regulation of molecular markers involved in angiogenesis using in-vivo and in-vitro models. BR treatment showed a significant reduction in Factor VIII expression compared to control indicating reduced angiogenesis. BR treated tumor specimens showed a decrease in the pro-angiogenic factors like VEGF, MMP-9 and MMP-2. Methanolic extract of BR was found to inhibit the proliferation, tube formation, cell migration and attachment of HUVEC on matrigel in a dose dependant manner. These findings suggest the possible mechanism(s) of action of BR in the reduction of tumor growth and metastatic spread.
目前前列腺癌的治疗方法包括根治性前列腺切除术、放射治疗和激素消融。化疗对一些晚期前列腺癌患者也有有益效果,但会产生一些有害的副作用。因此,需要识别和开发替代疗法,以在副作用最小或极少的情况下减缓疾病进展。我们实验室早期的研究表明,一种富含抗氧化成分的多草药混合物“梵天补养药(BR)”有可能成为一种抗肿瘤药物。用BR处理接种了MAT-LyLu细胞的哥本哈根大鼠,可使可触及肿瘤的发生率降低、肿瘤出现延迟且平均肿瘤体积减小。此外,与未处理的对照组相比,经BR处理的动物的肿瘤重量和肺转移也显著减少。在本研究中,我们重点使用体内和体外模型来研究BR对血管生成以及参与血管生成的分子标志物调控的影响。与对照组相比,BR处理显示因子VIII表达显著降低,表明血管生成减少。经BR处理的肿瘤标本中促血管生成因子如VEGF、MMP-9和MMP-2减少。发现BR的甲醇提取物以剂量依赖的方式抑制人脐静脉内皮细胞(HUVEC)在基质胶上的增殖、管形成、细胞迁移和附着。这些发现提示了BR在减少肿瘤生长和转移扩散方面可能的作用机制。