Experimental evidence of good efficacy and reduced toxicity with peptide-doxorubicin to treat gastric cancer
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Jue Zhang1,2,3, Jing-Ping Yuan3, Qun Wang3, Li-Hua Shao3, Shao-Ping Liu3, Raymond A. Firestone4, Ya-Ping Hong4, Ji-Guo Li4, Yan-Chao Xin5 and Yan Li1,3
1Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, P.R. China
2Department of Gynecologic Oncology, Hubei Maternal and Child Hospital, Wuhan 430071, P.R.China
3Department 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
4Nanjing Meihua Pharmaceuticals Ltd., Nanjing 210009, P.R. China
5Princeton Globalsynthesis LLC, Bristol, PA 19007, USA
Yan Li, email: [email protected]
Keywords: molecular targeted therapy; peptide-doxorubicin; prodrug; gastric cancer; experimental study
Received: September 11, 2017 Accepted: October 30, 2017 Published: December 14, 2017
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) in both subcutaneous and orthotopic models. Animal survival was much better in PDOX group than DOX group. In peripheral blood test, PDOX group had significantly higher levels of platelets than the Control (P < 0.05), and lymphocyte lower than Control (P < 0.05). There were no significant differences on liver, kidney and cardiac function parameters among three groups (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.
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