159 Alexandria Journal of Veterinary Sciences www.alexjvs.com AJVS. Vol. 61 (1): 159-167. April 2019 DOI: 10.5455/ajvs.29544 Assessment of Autophagy as Possible Mechanism of the Antitumor Effects of Arsenic Trioxide and/or Cisplatin on Ehrlich Ascites Carcinoma Model Mohammed A. Mansour 1,2 , Afrah F. Salama 1,* , Wafaa M. Ibrahim 3 , Eman S. Shalaan 1 1 Biochemistry Division, Department of Chemistry, Faculty of Science, Tanta University, Tanta, 31527, Egypt 2 Cancer Research UK Beatson Institute, Switchback Road, Glasgow, G61 1BD, UK; Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK. 3 Medical Biochemistry Department, Faculty of Medicine, Tanta University, Egypt. 1. INTRODUCTION Arsenic trioxide (ATO), have a noticeable therapeutic effect on solid tumor cell, lines, such as cervical cancer cells, human sarcoma cells, hepatoblastoma cells and HCC cells. ATO treatment activated both p38 MAPK and JNK pathway in Hela cells. Activation of MAPKs, such as p38 MAPK and JNK, were important for cancer prevention by drug therapy against cancer (Xia et al., 2018). Autophagy is a lysosome-dependent cellular degradation process that has functions in nutrient recycling and energy generation. Damaged proteins and organelles were clearance by this process. ABSTRACT Key words: Ehrlich ascites carcinoma – autophagy - arsenic trioxide -Cisplatin. Arsenic trioxide (As 2 O 3 ) (ATO) and Cisplatin (CIS) have potent antineoplastic effects in several types of cancer. Autophagy is important for normal cell function and survival, it is also used by tumor cells so, and we studied its role as possible mechanism of ATO and/or CIS antitumor effect on mice bearing Ehrlich Ascites carcinoma (EAC) and checked whether ATO can enhance the antitumor potential of CIS. The study was carried out on eight groups of female mice; GP1 (negative control), GP2 (Erlich tumor only), GP3 (Normal +ATO), GP4 (Normal + CIS), GP5 (Normal + ATO+CIS), GP6 (EAC+ATO), GP7 (EAC+CIS) and GP8 (EAC +ATO+ CIS). In this study, viable cells were counted, where percentage of viability (%) was calculated. Flow cytometry of autophagosome was appointed. Glutathione S- transferase (GST) and catalase (CAT) enzymes activities, total thiol and malondialdehyde (MDA) concentrations in liver tissues were determined to evaluate the effects of these drugs. Treatment with ATO (GP6) induced a significant decrease in tumor volume and percentage of viability with best result in combination of ATO with low dose of CIS (GP8) against EAC. Our results showed that a reduction in fluorescence intensity of autophagosome marker that determined by flow cytometry especially in combination treated group (GP8). CAT, GST enzymes activities and total thiol level were decreased, while MDA level was increased in ATO treated group (GP6) and CIS treated group (GP7) as compared to EAC group. On the other hand, combining both ATO and CIS in EAC treated group (GP8) decreased MDA level and augmented the level of total thiol and activities of CAT and GST enzymes. Therefore, our result revealed that combination of ATO and CIS have anti-tumor effects against EAC better than each one alone. So, we recommended the combination of ATO with CIS treatment due to their synergetic effect on cancer *Corresponding to: Afrah Salama, Biochemistry Division Department of Chemistry Faculty of Science Tanta University E-mail: afrahsalama@yahoo.com. Received 10 Nov 2018 Revised 25 Dec 2018 Accepted 30 Dec 2018