Department of Biophysics, Panjab University, Chandigarh, India.
Mol Cell Biochem. 2012 Feb;361(1-2):217-28. doi: 10.1007/s11010-011-1106-9. Epub 2011 Oct 12.
Cancer research illustrated that combinatorial studies can provide significant improvement in safety and effectiveness over the monotherapy regimens. A combination of two drugs may restrain precancerous colon polyps, opening a new possible opportunity for chemoprevention of colon cancer. In this context, chemopreventive efficacy of a combination regimen of C-phycocyanin, a biliprotein present in Spirulina platensis, a cyanobacterium, which is a selective cycloxygenase-2 (COX-2) inhibitor and piroxicam, a traditional non-steroidal anti-inflammatory drug was considered in 1,2 dimethylhyadrazine (DMH)-induced colon carcinogenesis in rats. Western blotting, immunohistochemistry, DNA fragmentation, fluorescent staining, PGE(2) enzyme immunoassay, and carrageenan-induced paw edema test were performed along with morphological and histological analysis. DMH treatment showed a rich presence of preneoplastic lesions such as multiple plaque lesions, aberrant crypt foci, and well-characterized dysplasia. These features were reduced with piroxicam and C-phycocyanin administration. The number of apoptotic cells was featured prominently in all the groups compared with DMH. DMH treatment revealed intact high molecular weight genomic DNA with no signs of laddering/DNA fragmentation while it was noticeable significantly in control and DMH + piroxicam + C-phycocyanin. DMH group showed highest COX-2 expression and PGE(2) level in comparison with other groups. Doses of piroxicam and C-phycocyanin used in the present study were established at an anti-inflammatory range. A combination regimen of piroxicam and C-phycocyanin, rather than individually has the much greater potential for reduction of DMH-induced colon cancer development and COX-2 being the prime possible target in such chemoprevention.
癌症研究表明，联合研究可以在安全性和有效性方面比单药治疗方案有显著提高。两种药物的联合可能会抑制癌前结肠息肉，为结肠癌的化学预防开辟新的可能机会。在这种情况下，考虑了蓝藻螺旋藻中存在的一种藻蓝蛋白 C-藻蓝蛋白与传统非甾体抗炎药吡罗昔康的组合方案对 1,2-二甲基肼（DMH）诱导的大鼠结肠癌发生的化学预防功效。进行了 Western blot、免疫组织化学、DNA 片段化、荧光染色、PGE（2）酶免疫测定和角叉菜胶诱导的爪肿胀试验以及形态学和组织学分析。DMH 处理显示出丰富的癌前病变，如多个斑块病变、异常隐窝焦点和特征性发育不良。这些特征随着吡罗昔康和 C-藻蓝蛋白的给药而减少。与 DMH 相比，所有组的细胞凋亡数量都很明显。DMH 处理显示完整的高分子量基因组 DNA，没有梯状/DNA 片段化的迹象，而在对照组和 DMH+吡罗昔康+C-藻蓝蛋白中则明显可见。与其他组相比，DMH 组显示出最高的 COX-2 表达和 PGE（2）水平。本研究中使用的吡罗昔康和 C-藻蓝蛋白的剂量处于抗炎范围内。与单独使用相比，吡罗昔康和 C-藻蓝蛋白的联合方案具有更大的潜力来减少 DMH 诱导的结肠癌发展，而 COX-2 可能是这种化学预防的主要靶标。
