Speakers - CIRWC 2024

Crisalde Ramirez Celis

  • Designation: PhD Student, Biomedicine, National Autonomous University of Mexico (UNAM)
  • Country: Mexico
  • Title: Effect of Zidovudine (AZT), Adenosine (ADO) and their Coadministration in Hepatic Cells

Abstract

Liver cancer ranks seventh in morbidity and third in mortality among the different types of cancer and is the 5th most frequent malignant tumour in men and the 9th in women worldwide (1). There are different types of liver cancer depending on the type of cancerous cells. Hepatocellular carcinoma (HCC) is the most frequent, representing approximately 90% of primary liver cancers and is one of the most frequent and leading causes of mortality worldwide (2, 3). The treatment of HCC is based on immunotherapy and chemotherapy, being the best therapeutic options [4]. Chemotherapeutics can be administered alone or in combination with other drugs; however, prolonged administration of these can lead to hepatotoxicity, which can be due to damage to structures such as hepatic sinusoids, bile duct vasculature, and direct damage to hepatocytes [5, 6, 7]. This project aimed to evaluate the effect of adenosine (ADO) and zidovudine (AZT) on the proliferation of Hep-G2 cancer cell lines both individually and in coadministration. Our results have demonstrated that the coadministration of ADO and AZT in coadministration have a synergistic effect by decreasing the % of the viability of Hep-G2 cells. To understand this effect, we evaluated apoptosis and the cell cycle, observing that when we administered both ADO and AZT, there was an increment in the cells in apoptosis with very few cells with necrosis. Similar results were observed when evaluating the cell cycle, demonstrating that when we administered both drugs, there was a cell cycle arrest both in G1 and S phases. When evaluating the expression of proteins involved in these two processes, we determined that the word of p21, p27, and BAX were overexpressed when treating the cells with ADO and AZT; meanwhile, the expression of cyclin B, BAD were inhibited after 48h of treatment in comparison with cells treated only for 24h. These results increase the knowledge of the combination of ADO and AZT for future application in liver cancer therapeutics. 

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