临床毒理学杂志
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Prognosis of Hepatocellular Carcinoma with the Detection of Glypican 3 and its Inhibition by Triptolide using Docking Studies with Autodock Vina

Iffat Ara*, Burhan Khatri, Qurat Ul Ain Chaudhary, Shakeel Ahmed, Khadija Makkiah

Intake of fluoridated water can be one of the most common neglected factors affecting the livers of individuals. Hepatocellular Carcinoma (HCC) is the most common malignant tumor responsible for a large number of deaths globally. Surveillance requires the early detection of HCC among patients at the first stage of cancer. The study aimed at the prognosis of HCC for which the Glypican-3 (GPC3) biomarker was used. Fluoride content in drinking water and serum of populations from district Narowal (sample) and DHA Lahore (control) was measured by the ion-selective electrode. The levels of expression of GPC3 in both samples and controls were determined by ELISA. The binding affinity of triptolide to glypican 3 using AutoDock Vina was determined by hydrogen bonds, binding energy, and clusters of interacting amino acid residues using discovery studio. Results analyzed by student’s t-test showed a significant increase (p=0.0001) in GPC3 with rising fluoride content in sample water and serum samples. Ligand binding modes with glypican3 showed the highest binding affinity (Δ -7.1 kcal/mol) with the lowest RMSD (0.000) by Autodock Vina. The study proves that the long-term consumption of fluoridated water is one of the leading causes of HCC that can be diagnosed at early stages by the detection of glypican 3 levels. Further, binding of triptolide to glypican3 in nonspecific manner demands structurally modified pharmacological targets for the prevention of HCC.