Increasing the radiation-induced cytotoxicity by silver nanoparticles and docetaxel in prostate cancer cells

Mol Biol Rep. 2024 May 9;51(1):633. doi: 10.1007/s11033-024-09506-5.

Abstract

Background: Radiation therapy is utilized for treatment of localized prostate cancer. Nevertheless, cancerous cells frequently develop radiation resistance. While higher radiation doses have not always been effective, radiosensitizers have been extensively studied for their ability to enhance the cytotoxic effects of radiation. So, this study aims to evaluate the possible radiosensitization effects of docetaxel (DTX) and silver nanoparticles (SNP) in LNCaP cells.

Methods: The cytotoxic effects of DTX, SNP and 2 Gy of X-Ray radiation treatments were assessed in human LNCaP cell line using the MTT test after 24 h. Moreover, the effects of DTX, SNP and radiation on Epidermal growth factor (EGF), Caspase 3, inducible nitric oxide synthase and E-cadherin gene expression were analyzed using the Real-time PCR method. The level of Hydrogen peroxide (H2O2), an oxidative stress marker, was also detected 24 h after various single and combined treatments.

Results: The combinations of SNP (in low toxic concentration) and/or DTX (0.25× IC50 and 0.5 × IC50 concentrations for triple and double combinations respectively) with radiation induced significant cytotoxicity in LNCaP cells in comparison to monotherapies. These cytotoxic effects were associated with the downregulation of EGF mRNA. Additionally, H2O2 levels increased after Radiation + SNP + DTX triple combination and double combinations including Radiation + SNP and Radiation + DTX versus single treatments. The triple combination treatment also increased Caspase 3 and and E-cadherin mRNA levels in compared to single treatments in LNCaP cells.

Conclusion: Our results indicate that the combination of SNP and DTX with radiation induces significant anti-cancer effects. Upregulation of Caspase 3 and E-cadherin gene expression, and decreased mRNA expression level of EGF may be exerted specifically by use of this combination versus single treatments.

Keywords: Docetaxel; Prostate cancer; Radiation; Silver nanoparticle.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Cadherins / genetics
  • Cadherins / metabolism
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Docetaxel* / pharmacology
  • Epidermal Growth Factor / metabolism
  • Epidermal Growth Factor / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Male
  • Metal Nanoparticles*
  • Oxidative Stress / drug effects
  • Oxidative Stress / radiation effects
  • Prostatic Neoplasms* / drug therapy
  • Prostatic Neoplasms* / genetics
  • Prostatic Neoplasms* / metabolism
  • Prostatic Neoplasms* / radiotherapy
  • Radiation-Sensitizing Agents* / pharmacology
  • Silver* / pharmacology

Substances

  • Docetaxel
  • Silver
  • Radiation-Sensitizing Agents
  • Hydrogen Peroxide
  • Caspase 3
  • Antineoplastic Agents
  • Epidermal Growth Factor
  • Cadherins