Oncotarget

Research Papers:

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

Jue Zhang, Jing-Ping Yuan, Qun Wang, Li-Hua Shao, Shao-Ping Liu, Raymond A. Firestone, Ya-Ping Hong, Ji-Guo Li, Yan-Chao Xin and Yan Li _

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Oncotarget. 2018; 9:1957-1968. https://doi.org/10.18632/oncotarget.23319

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Abstract

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

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) 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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