Yang Chih-Yung, Liu Hong-Wen, Tsai Ya-Ching, Tseng Ju-Yu, Liang Shu-Ching, Chen Chin-Yau, Lian Wei-Nan, Wei Ming-Cheng, Lu Maggie, Lu Ruey-Hwa, Lin Chi-Hung, Jiang Jeng-Kai
a Department of Education and Research ; Taipei City Hospital ; Taipei , Taiwan.
b Institute of Microbiology and Immunology, National Yang-Ming University ; Taipei , Taiwan.
Cancer Biol Ther. 2015;16(11):1641-50. doi: 10.1080/15384047.2015.1095397. Epub 2015 Oct 5.
Our previous studies showed that colorectal tumor has high interleukin-4 receptor α (IL-4Rα) expression, whereas adjacent normal tissue has low or no IL-4Rα expression. We also observed that human atherosclerotic plaque-specific peptide-1 (AP1) can specifically target to IL-4Rα. In this study, we investigated the therapeutic efficacy and systemic toxicity of AP1-conjuagted liposomal doxorubicin. AP1 bound more strongly to and was more efficiently internalized into IL-4Rα-overexpressing CT26 cells than CT26 control cells. Selective cytotoxicity experiment revealed that AP1-conjugated liposomal doxorubicin preferentially killed IL-4Rα-overexpressing CT26 cells. AP1-conjugated liposomal doxorubicin administered intravenously into mice produced significant inhibition of tumor growth and showed decreased cardiotoxicity of doxorubicin. These results indicated that AP1-conjugated liposomal doxorubicin has a potent and selective anticancer potential against IL-4Rα-overexpressing colorectal cancer cells, thus providing a model for targeted anticancer therapy.
我们之前的研究表明，结直肠癌组织中白细胞介素-4受体α（IL-4Rα）表达较高，而相邻的正常组织中IL-4Rα表达较低或无表达。我们还观察到，人动脉粥样硬化斑块特异性肽-1（AP1）可特异性靶向IL-4Rα。在本研究中，我们调查了AP1偶联脂质体阿霉素的治疗效果和全身毒性。与CT26对照细胞相比，AP1与IL-4Rα过表达的CT26细胞结合更紧密，且更有效地内化进入细胞。选择性细胞毒性实验表明，AP1偶联脂质体阿霉素优先杀死IL-4Rα过表达的CT26细胞。静脉注射AP1偶联脂质体阿霉素可显著抑制小鼠肿瘤生长，并降低阿霉素的心脏毒性。这些结果表明，AP1偶联脂质体阿霉素对IL-4Rα过表达的结直肠癌细胞具有强大的选择性抗癌潜力，从而为靶向抗癌治疗提供了一个模型。
