LDR reverses DDP resistance in ovarian cancer cells by affecting ERCC-1, Bcl-2, Survivin and Caspase-3 expressions

Biomed Pharmacother. 2018 Jun:102:549-554. doi: 10.1016/j.biopha.2018.03.092. Epub 2018 Apr 5.

Abstract

Background: Ovarian cancer is the most frequent cause of death resulting from malignant gynecological tumors. After surgical intervention, cisplatin (DDP) is a major chemotherapy drug for ovarian cancer, but the ovarian cancer cells tend to develop DDP resistance in the clinical setting. Tumor cells are sensitive to low-dose radiation (LDR). However, how the LDR therapy improves the effects of chemotherapy drugs on ovarian cancer is not well understood. This study aimed to explore this issue.

Methods: The SKOV3/DDP cells were divided into 3 groups, including low-dose group, conventional-dose group, and control group (no radiation). Cell counting kit-8 assay was performed to measure cell proliferation. Flow cytometric analysis was then utilized to quantify the apoptosis with classical Annexin V/propidium iodide co-staining. And Real-time quantitative PCR and western blot were eventually used to analyze the mRNA and protein levels of excision repair cross complementing-group 1 (ERCC1), B-cell lymphoma 2 (Bcl-2), Survivin and Caspase-3, respectively.

Results: The IC50 value of DDP in the low-dose group was significantly lower compared with the other two groups. Compared with the conventional-dose group and control group, LDR treatment resulted in significantly more apoptosis. Besides, LDR treatment significantly decreased the mRNA and protein expression of ERCC1, Bcl-2, and Survivin, and enhanced the mRNA and protein expression of Caspase-3 compared with the other two groups.

Conclusions: LDR reversed DDP resistance in SKOV3/DDP cells possibly by suppressing ERCC1, Bcl-2, and Survivin expressions, and increasing Caspase-3 expression.

Keywords: B-Cell lymphoma 2 (Bcl-2); Caspase-3; Cisplatin (DDP); Excision repair cross complementing-group 1 (ERCC1); Low-dose radiation (LDR); SKOV3/DDP cells; Survivin.

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Caspase 3 / genetics
  • Caspase 3 / metabolism*
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Dose-Response Relationship, Radiation
  • Drug Resistance, Neoplasm* / drug effects
  • Drug Resistance, Neoplasm* / radiation effects
  • Endonucleases / genetics
  • Endonucleases / metabolism*
  • Female
  • Humans
  • Inhibitor of Apoptosis Proteins / genetics
  • Inhibitor of Apoptosis Proteins / metabolism*
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Survivin
  • X-Rays

Substances

  • BIRC5 protein, human
  • DNA-Binding Proteins
  • Inhibitor of Apoptosis Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Survivin
  • ERCC1 protein, human
  • Endonucleases
  • Caspase 3
  • Cisplatin