The Anticancer Efficacy of Platinum Azidothymidin on Hepatocellular Carcinoma Via Affecting the Telomerase and the BcL-2 Genes Expression

J Gastrointest Cancer. 2020 Sep;51(3):813-817. doi: 10.1007/s12029-019-00296-9.

Abstract

Purpose: The study of correlation between cancer biomarkers after treatment with anticancer drugs would represent a promising insight into the effectiveness of the drug.

Methods: In this study, after induction of hepatocellular carcinoma, rats were divided into four groups: groups A and B as healthy or control group and negative untreated cancer group respectively; groups C and D were treated with platinum azido-thymidine (0.9 mg/kg/day), a novel anti-cancer drug, and azido-thymidine (AZT) (0.3 mg/kg/day) respectively. After induction of cancer, the telomerase and Bcl-2 expression were evaluated by real-time PCR (RT-qPCR), and also Bcl-2 concentration and telomerase activity were measured by enzyme-linked immunosorbent assay (ELISA) and telomerase repeat amplification protocol (TRAP) respectively.

Results: A significant correlation was observed between telomerase and Bcl-2 in untreated HCC-induced rats as compared to the control group. In untreated cancer group, a direct significant correlation between telomerase activity and expression (r = 0.453, p = 0.022*) and also a negative significant correlation between telomerase activity and Bcl-2 concentration (r = - 0.43, p = 0.034*) and also between telomerase and Bcl-2 expression (r = - 0.088, p = 0.006*) was observed. In drug-treated groups, there was a significant negative correlation between telomerase expression and Bcl-2 concentration (r = - 0.45, p = 0.025) only in the AZT-treated groups.

Conclusion: Our results indicated a correlation between cancer factors in the untreated cancerous group B and in treated groups only limited to the azithoimidin-treated group (group D). Hence, it may be possible to use this strategy to develop remarkable anticancer drugs in future studies, though this hypothesis requires more in-depth research.

Keywords: Azidothymidine; Bcl-2; Hepatocellular carcinoma; Platinum azidothymidin; Telomerase.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Hepatocellular / chemically induced
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / pathology
  • Drug Screening Assays, Antitumor
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Liver / drug effects
  • Liver / pathology
  • Liver Neoplasms, Experimental / chemically induced
  • Liver Neoplasms, Experimental / drug therapy*
  • Liver Neoplasms, Experimental / pathology
  • Male
  • Platinum / chemistry
  • Platinum / pharmacology
  • Platinum / therapeutic use
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Telomerase / analysis
  • Telomerase / metabolism
  • Zidovudine / chemistry
  • Zidovudine / pharmacology
  • Zidovudine / therapeutic use

Substances

  • Antineoplastic Agents
  • Bcl2 protein, rat
  • Biomarkers, Tumor
  • Proto-Oncogene Proteins c-bcl-2
  • Platinum
  • Zidovudine
  • Telomerase
  • Tert protein, rat