Zinc enhances chemosensitivity to paclitaxel in PC‑3 prostate cancer cells

Oncol Rep. 2018 Oct;40(4):2269-2277. doi: 10.3892/or.2018.6622. Epub 2018 Aug 2.

Abstract

Paclitaxel‑based chemotherapy is a promising approach for prostate cancer treatment. However, single‑drug chemotherapy is associated with an increased risk of drug resistance. Therefore, novel combination chemotherapy regimens are a popular topic of research. Zinc participates in the regulation of apoptosis, for example in the form of Zn2+ and via zinc‑dependent enzymes. Zinc can either induce or suppress apoptosis, and its effect depends primarily on its concentration. Previous research has demonstrated that physiological concentrations of zinc can directly induce apoptosis of PC‑3 prostate cancer cells via the mitochondrial pathway. In prostate cancer tissues, zinc concentrations have been demonstrated to be reduced compared with non-cancerous tissues. Furthermore, the concentration of zinc has been demonstrated to decrease further with cancer progression. In the present study, it was investigated whether exposure of PC‑3 cells to zinc improved their sensitivity to the chemotherapeutic agent, paclitaxel. MTT assays, cell clone formation assays, Hoechst staining and flow cytometry revealed that zinc enhanced PC‑3‑cell chemosensitivity to paclitaxel. Western blotting and reverse transcription‑polymerase chain reaction were used to determine that the mitochondria‑mediated apoptosis signaling pathway is involved with zinc/paclitaxel‑induced cell death. The present study provides a foundation for the development of novel tumor combination therapy.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Cell Proliferation / drug effects
  • Drug Resistance, Neoplasm / drug effects*
  • Humans
  • Male
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mitochondria / pathology*
  • Paclitaxel / pharmacology*
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Tumor Cells, Cultured
  • Zinc / pharmacology*

Substances

  • Antineoplastic Agents, Phytogenic
  • Zinc
  • Paclitaxel