Efficacy and Safety Evaluation of Combination Treathment with Endostar and Cisplatin in Malignant Peritoneal Effusion

doi:10.3969/j.issn.1674-5817.2018.03.006

Abstract

Abstract: Objective To evaluate efficacy of the combination of Endostar and cisplatin in malignant peritoneal effusion and its underlying mechanism(s).Methods The H22 tumor ascites mice model was successfully established and randomly divided into control group,Endostar group (10 mg/kg/day),cisplatin group (2.5 mg/kg/5 day),combination group 1(Endostar was given every day) and combination group2 (Endostar was given every 2 days).Each group consist of 18 animals.At the end of the treatment,6 animals in each group were sacrificed.The ascites volume,erythrocytes number in ascites,number and apoptosis rate of tumor cells in ascites were recorded.The survival time was observed and the endpoint was determined as all control animals died.Results (1) Compared with the saline group,the body weight,the growth rate of the abdominal circumference and the ascites volume were significantly decreased in the Endostar group,cisplatin group and the Endostar-cisplatin combination group (P<0.01).The growth rate in the body weight and abdominal circumference and ascites volume were significantly lower than those in the Endostar group and the cisplatin group (P<0.01).(2) The number of erythrocytes in Endostar-cisplatin combination group 2 was significantly lower than that in saline group,Endostar group and cisplatin group (P<0.01).The number of tumor cells in the ascites of the saline group was significantly higher than that in the Endostar group,the cisplatin group and the Endostar-cisplatin combination group (P<0.01).The apoptosis rate of tumor cells in Endostar-cisplatin combined group was significantly higher than that in saline group and Endostar group (P<0.01),There was no significant difference between control and cisplatin group.(3) Log-rank analysis showed that combination group had a significant effect on the survival time of mice (P<0.01).Conclusion The combination of Endostar and cisplatin effectively inhibits the production of ascites,reduces the red blood cell permeability,and induces the apoptosis of tumor cells in ascites,which may extend the survival time of animal.The two drugs has synergistic effect.The effect of daily administration of Endostar is better than administration each other day.

Key words: Endostar, Cisplatin, Malignant peritoneal effusion, Efficacy evaluation

CLC Number:

Q95-33

YAN Jun, LU Guo-feng, WANG Chun, MIN Xin. Efficacy and Safety Evaluation of Combination Treathment with Endostar and Cisplatin in Malignant Peritoneal Effusion[J]. Laboratory Animal and Comparative Medicine, 2018, 38(3): 194-201.

References

[1] Le Corvec M,Jezequel C,Monbet V,et al.Mid-infrared spectroscopy of serum,a promising non-invasive method to assess prognosis in patients with ascites and cirrhosis[J].PLoS One,2017,12(10):e0185997.
[2] Bekes I,Friedl TW,Kohler T,et al.Does VEGF facilitate local tumor growth and spread into the abdominal cavity by suppressing endothelial cell adhesion,thus increasing vascular peritoneal permeability followed by ascites production in ovarian cancer?[J].Mol Cancer,2016,15:13.
[3] O'Reilly MS,Boehm T,Shing Y,et al.Endostatin:an endogenous inhibitor of angiogenesis and tumor growth[J].Cell,1997,88(2):277-285.
[4] Zhang YC,Li XM,Yu Z,et al.Efficacy of pEgr-1-endostatin combined with ionizing radiation on hypoxic conditions in nude mice bearing SKOV3 ovarian carcinoma[J].Oncol Lett,2017,13(3):1101-1108.
[5] Ren Z,Wang Y,Jiang W,et al.Anti-tumor effect of a novel soluble recombinant human endostatin:administered as a single agent or in combination with chemotherapy agents in mouse tumor models[J].PLoS One,2014,9(9):e107823.
[6] Tong Y,Zhong K,Tian H,et al.Characterization of a monoPEG20000-Endostar[J].Int J Biol Macromol,2010,46(3):331-336.
[7] Zhang Q,Cao J,Xue K,et al.Recombinant human endostatin in combination with CHOP regimen for peripheral T cell lymphoma[J].Onco Targets Ther,2017,10:145-151.
[8] Biaoxue R,Xiguang C,Hua L,et al.Thoracic perfusion of recombinant human endostatin (Endostar) combined with chemotherapeutic agents versus chemotherapeutic agents alone for treating malignant pleural effusions:a systematic evaluation and meta-analysis[J].BMC Cancer,2016,16(1):888.
[9] Hochster HS,Piccart M.Intraperitoneal chemotherapy:belly bath or pain in the side[J].Eur J Cancer Clin Oncol,1987,23(3):259-261.
[10] Hirayama N,Tabata C,Tabata R,et al.Pleural effusion VEGF levels as a prognostic factor of malignant pleural mesothelioma[J].Respir Med,2011,105(1):137-142.
[11] Abdel-Razik A,Mousa N,Elalfy H,et al.A novel combination of C-reactive protein and vascular endothelial growth factor in differential diagnosis of ascites[J].J Gastrointest Cancer,2017,48(1):50-57.
[12] Yin T,Wang G,He S,et al.Malignant pleural effusion and ascites induce epithelial-mesenchymal transition and cancer stem-like cell properties via the vascular endothelial growth factor (VEGF)/phosphatidylinositol 3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) Pathway[J].J Biol Chem,2016,291(52):26750-26761.
[13] Yang L,Zhang Y,Cheng L,et al.Mesenchymal stem cells engineered to secrete pigment epithelium-derived factor inhibit tumor metastasis and the formation of malignant ascites in a murine colorectal peritoneal carcinomatosis model[J].Hum Gene Ther,2016,27(3):267-77.
[14] Wei H,Qin S,Yin X,et al.Endostar inhibits ascites formation and prolongs survival in mouse models of malignant ascites[J].Oncol Lett,2015,9(6):2694-2700.
[15] Mostmans Y,Cutolo M,Giddelo C,et al.The role of endothelial cells in the vasculopathy of systemic sclerosis:A systematic review[J].Autoimmun Rev,2017,16(8):774-786.
[16] Han Q,Fu Y,Zhou H,et al.Contributions of Zn(II)-binding to the structural stability of endostatin[J].FEBS Lett,2007,581(16):3027-3032.
[17] Mohajeri A,Sanaei S,Kiafar F,et al.The challenges of recombinant endostatin in clinical application:focus on the different expression systems and molecular bioengineering[J].Adv Pharm Bull,2017,7(1):21-34.