Experimental evidence of good efficacy and reduced toxicity with peptide-doxorubicin to treat gastric cancer

// Jue Zhang 1, 2, 3 , Jing-Ping Yuan 3 , Qun Wang 3 , Li-Hua Shao 3 , Shao-Ping Liu 3 , Raymond A. Firestone 4 , Ya-Ping Hong 4 , Ji-Guo Li 4 , Yan-Chao Xin 5 and Yan Li 1, 3 1 Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, P.R. China 2 Department of Gynecologic Oncology, Hubei Maternal and Child Hospital, Wuhan 430071, P.R.China 3 Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, Wuhan 430071, P.R. China 4 Nanjing Meihua Pharmaceuticals Ltd., Nanjing 210009, P.R. China 5 Princeton Globalsynthesis LLC, Bristol, PA 19007, USA Correspondence to: Yan Li, email: liyansd2@163.com Keywords: molecular targeted therapy; peptide-doxorubicin; prodrug; gastric cancer; experimental study Received: September 11, 2017      Accepted: October 30, 2017      Published: December 14, 2017 ABSTRACT Background: To compare the efficacy and toxicity of peptide-doxorubicin (PDOX) and doxorubicin (DOX) on nude mice models of human gastric cancer. Results: Both PDOX and DOX could significantly inhibit tumor growth compared with Control ( P 0.05). Immunohistochemistry showed that treatment groups had much higher Tunel than Control ( P < 0.05), and PDOX had significantly lower Ki-67 than doxorubicin and Control group ( P < 0.01). Western blotting showed that PDOX caused much higher expressions of P53, P21, Aparf-1, pro- and cleaved-caspase 3, compared with DOX. Conclusion: Compared with DOX, PDOX has increased effects but much decreased toxicity in treating animal model of gastric cancer. Materials and Methods: Animals in subcutaneous model were randomized into Control, doxorubicin, PDOX-L, PDOX-M, and PDOX-H groups. Animals in surgical orthotopic implantation model were randomized into Control, doxorubicin and, peptide-doxorubicin groups. The animals were treated, monitored and examined following a set protocol.