Mathivadhani P, Shanthi P, Sachdanandam P
Department of Medical Biochemistry, DR. A.L.M. Post-Graduate, Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600113, India.
Vascul Pharmacol. 2007 Jun;46(6):419-26. doi: 10.1016/j.vph.2006.12.004. Epub 2007 Jan 13.
The early stages of invasion are characterized by the extracellular proteolysis and the accumulation of specialized extracellular matrix (ECM) scaffold, that are responsible for the development of vascular bed, endothelial cell proliferation and invasion of tumour cells. The ground substance of provisional matrix consists of collagen, elastin, glycoaminoglycans and proteoglycans that facilitate the interaction of tumour cells with the host environment. In the present work, we have studied the influence of Semecarpus anacardium nut milk extract on localized differentials of ECM component and proteases involved in matrix metabolism of tumour tissue. Mammary carcinoma was induced in Sprague Dawley rats with 7,12, dimethyl benz(a)anthracene and treated with S. anacardium nut milk extract administered orally for 14 days. The altered amount of ECM components in tumour tissues was almost reverted back to normal level in the drug treated animals. The activities of reported proteases and glycohydrolases were also decreased on treatment with S. anacardium nut milk extract indicating decreased turnover of the matrix. Also, the factors associated with the matrix turnover and expression of MMP-1, MMP-2, MMP-3, TIMP-1 and TIMP-2 were restored back to near normal values. The stabilization of the ECM with the decreased activity of proteases might inhibit the epithelial-endothelial interaction and tumour cell migration thus, preventing the adjacent invasion and tumour growth and might be regarded as antineoplastic agent which demands further studies.
侵袭的早期阶段以细胞外蛋白水解和特殊细胞外基质（ECM）支架的积累为特征，这些过程负责血管床的发育、内皮细胞增殖以及肿瘤细胞的侵袭。临时基质的基质成分包括胶原蛋白、弹性蛋白、糖胺聚糖和蛋白聚糖，它们促进肿瘤细胞与宿主环境的相互作用。在本研究中，我们研究了印度没药坚果奶提取物对肿瘤组织基质代谢中ECM成分和蛋白酶局部差异的影响。用7,12-二甲基苯并(a)蒽诱导Sprague Dawley大鼠发生乳腺癌，并用印度没药坚果奶提取物口服治疗14天。在药物治疗的动物中，肿瘤组织中ECM成分的改变量几乎恢复到正常水平。在用印度没药坚果奶提取物治疗后，所报道的蛋白酶和糖苷水解酶的活性也降低，表明基质周转率降低。此外，与基质周转以及MMP-1、MMP-2、MMP-3、TIMP-1和TIMP-2表达相关的因子恢复到接近正常的值。蛋白酶活性降低导致的ECM稳定可能会抑制上皮-内皮相互作用和肿瘤细胞迁移，从而防止肿瘤的邻近侵袭和生长，可能被视为一种需要进一步研究的抗肿瘤药物。
