Anti-tumour activity and toxicological studies of combination treatment of Orthosiphon stamineus and gemcitabine on pancreatic xenograft model  

作　　者：Ashwaq Hamid Salem Yehya Ayappa V Subramaniam Muhammad Asif Gurjeet Kaur Amin M S Abdul Majid Chern Ein Oon 

机构地区：[1]Institute for Research in Molecular Medicine,Universiti Sains Malaysia,Penang 11800,Malaysia [2]Cancer Research,Eman Biodiscoveries,Kedah 08000,Malaysia [3]Department of Pharmacology,Faculty of Pharmacy,The Islamia University of Bahawalpur,Punjab 63100,Pakistan [4]Department of Cancer Biology and Therapeutics,The John Curtin School of Medical Research,Australia 2601,Australia

出　　处：《World Journal of Gastroenterology》2022年第32期4620-4634,共15页世界胃肠病学杂志（英文版）

基　　金：Supported by the NKEA Research Grant Scheme (NRGS) by the Ministry of Agriculture Malaysia;No. 304/CIPPM/650736/k123

摘　　要：BACKGROUND Pancreatic cancer is the most aggressive cancer type.Gemcitabine is the first line chemo-drug used for pancreatic cancer but exerts a broad spectrum of organ toxicities and adverse effects in patients.AIM To evaluate the anti-tumour activity and toxicological effects of Orthosiphon stamineus extract formulation(ID:C5EOSEW5050ESA trademarked as Nuvastatic^(TM)),and gemcitabine combination on pancreatic xenograft model.METHODS Mice were randomly divided into six groups of 6 mice each(n=6)and given different treatments for 28 d.The study design consisted of a 2 x 3 factorial treatment structure,with gemcitabine(yes/no)by oral(at 1200 and 400 mg/kg per day).Human pancreatic cancer cells were injected subcutaneously into the flanks of athymic nude mice.C5EOSEW5050ESA(200 or 400 mg/kg per day)was administered orally,while gemcitabine(10 mg/kg per 3 d)was given intraperitoneally either alone or in combination treatment.Histopathological analyses of vital organs,tumour tissues,and incidence of lethality were analysed.Analyses of tumour necrosis and proliferation were determined by haematoxylin-eosin staining and immunohistochemistry for Ki-67,respectively.RESULTS No signs of toxicity or damage to vital organs were observed in all treatment groups compared to the untreated group.C5EOSEW5050ESA at 200 mg/kg and gemcitabine combination had no additive antitumor effects compared to a single treatment.Remarkably,a comparably greater response in a reduction in tumour growth,Ki-67 protein expression,and necrosis was demonstrated by 400 mg/kg of C5EOSEW5050ESA and gemcitabine combination than that of the individual agents.CONCLUSION These results highlighted the synergistic activity of C5EOSEW5050ESA with gemcitabine to reduce pancreatic tumour growth in mice compared to a single treatment.Thus,this study provides valuable insights into using C5EOSEW5050ESA as a complementary treatment with gemcitabine for pancreatic cancer.

关 键 词：Pancreatic cancer Orthosiphon stamineus C5EOSEW5050ESA GEMCITABINE Complementary medicine 

分 类 号：R735.9[医药卫生—肿瘤]