Zhang Jue, Yuan Jing-Ping, Wang Qun, Shao Li-Hua, Liu Shao-Ping, Firestone Raymond A, Hong Ya-Ping, Li Ji-Guo, Xin Yan-Chao, Li Yan
Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, P.R. China.
Department of Gynecologic Oncology, Hubei Maternal and Child Hospital, Wuhan 430071, P.R.China.
Oncotarget. 2017 Dec 14;9(2):1957-1968. doi: 10.18632/oncotarget.23319. eCollection 2018 Jan 5.
To compare the efficacy and toxicity of peptide-doxorubicin (PDOX) and doxorubicin (DOX) on nude mice models of human gastric cancer.
Both PDOX and DOX could significantly inhibit tumor growth compared with Control ( < 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 ( < 0.05), and lymphocyte lower than Control ( < 0.05). There were no significant differences on liver, kidney and cardiac function parameters among three groups ( > 0.05). Immunohistochemistry showed that treatment groups had much higher Tunel than Control ( < 0.05), and PDOX had significantly lower Ki-67 than doxorubicin and Control group ( < 0.01). Western blotting showed that PDOX caused much higher expressions of P53, P21, Aparf-1, pro- and cleaved-caspase 3, compared with DOX.
Compared with DOX, PDOX has increased effects but much decreased toxicity in treating animal model of gastric cancer.
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.
比较肽-阿霉素(PDOX)和阿霉素(DOX)对人胃癌裸鼠模型的疗效和毒性。
在皮下和原位模型中,与对照组相比,PDOX和DOX均能显著抑制肿瘤生长(P<0.05)。PDOX组动物存活率远高于DOX组。外周血检测中,PDOX组血小板水平显著高于对照组(P<0.05),淋巴细胞水平低于对照组(P<0.05)。三组间肝、肾和心功能参数无显著差异(P>0.05)。免疫组化显示,治疗组Tunel水平远高于对照组(P<0.05),且PDOX组Ki-67水平显著低于阿霉素组和对照组(P<0.01)。蛋白质印迹法显示,与DOX相比,PDOX导致P53、P21、Aparf-1、前体和裂解的半胱天冬酶3的表达更高。
与DOX相比,PDOX在治疗胃癌动物模型中疗效增强但毒性大幅降低。
皮下模型动物随机分为对照组、阿霉素组、低剂量PDOX组、中剂量PDOX组和高剂量PDOX组。手术原位植入模型动物随机分为对照组、阿霉素组和肽-阿霉素组。按照既定方案对动物进行治疗、监测和检查。