Khan Arif, Khan Aijaz A, Dwivedi Varun, Ahmad Manzoor G, Hakeem Seema, Owais Mohammad
Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India.
Mol Med. 2007 May-Jun;13(5-6):266-76. doi: 10.2119/2007–00018.Khan.
Anticancer drugs are generally plagued by toxic manifestations at doses necessary for control of various forms of cancer. Incorporating such drugs into liposomes not only reduces toxicity but also enhances the therapeutic index. Some antioxidants and potent immunomodulators have also been shown to impart significant antitumor activity presumably by nonspecific activation of the host immune system. In the present study, we evaluated augmentation of the antitumor activity of etoposide (ETP) by the immunomodulator tuftsin in Swiss albino mice with fibrosarcoma. The efficacies of the free form of ETP, liposomized ETP (Lip-ETP), and tuftsin-bearing liposomized ETP (Tuft-Lip-ETP) formulations were evaluated on the basis of tumor regression, effect on expression level of p53wt and p53mut, and survival of the treated animals. Tuft-Lip-ETP, when administered at a dosage of 10 mg/kg body weight/day for five days, significantly reduced tumor volume, delayed tumor growth, and also up-regulated the expression of p53wt. In contrast, although Lip-ETP delayed tumor growth, it did not decrease tumor size. The results of the present study suggest that tuftsin incorporation in drug-loaded liposomes is a promising treatment strategy for various forms of cancers, including fibrosarcoma.
抗癌药物通常在控制各种癌症所需的剂量下会出现毒性表现。将此类药物包裹在脂质体中不仅可以降低毒性,还能提高治疗指数。一些抗氧化剂和强效免疫调节剂也已被证明可能通过非特异性激活宿主免疫系统而具有显著的抗肿瘤活性。在本研究中,我们评估了免疫调节剂促吞噬素对携带纤维肉瘤的瑞士白化小鼠中依托泊苷(ETP)抗肿瘤活性的增强作用。基于肿瘤消退、对p53野生型和p53突变型表达水平的影响以及治疗动物的存活情况,评估了游离形式的ETP、脂质体化ETP(Lip-ETP)和携带促吞噬素的脂质体化ETP(Tuft-Lip-ETP)制剂的疗效。当以10 mg/kg体重/天的剂量连续五天给予Tuft-Lip-ETP时,可显著减小肿瘤体积、延缓肿瘤生长,并上调p53野生型的表达。相比之下,尽管Lip-ETP延缓了肿瘤生长,但并未减小肿瘤大小。本研究结果表明,在载药脂质体中加入促吞噬素是包括纤维肉瘤在内的各种癌症的一种有前景的治疗策略。