α-Solanine Modulates the Radiosensitivity of Esophageal Cancer Cells by Inducing MicroRNA 138 Expression

Cell Physiol Biochem. 2016;39(3):996-1010. doi: 10.1159/000447807. Epub 2016 Aug 19.

Abstract

Background: Esophageal cancer (EC) is one of the most common malignant tumors in the world. Due to difficulties with performing the operation, most patients choose to have palliative treatment instead. Radiotherapy is one of the main palliative treatments of EC. However, the clinical efficacy of radiotherapy is not satisfactory α-Solanine is a bioactive component of steroidal glycoalkaloids which has been demonstrated to exhibit anti-metastasis activity in different cancers. In the present study, we determined the effect of α-solanine on the radiosensitivity of EC cells and priliminarily explored the underlying molecular mechanisms.

Methods: Cell Counting Kit-8 (CCK-8) assay was conducted to found the cytotoxic effect of α-solanine on EC cells. CCK-8 assay and colony-forming survival assays were performed to explore the effect of α-solanine on cell viability and proliferation of EC cells after irradiation. Immunofluorescence and comet assays were used to detect the effect of α-solanine on DNA repair capacity of EC cells after irradiation. The flow cytometry (FCM) and Hoechst/PI staining were conductd to study the effect of α-solanine on apoptosis of EC cells after irradiation.

Results: The cytotoxic effect of α-solanine to EC cells was dose-dependent. The results of CCK-8, colony-forming survival assay, immunofluorescence, comet assay, FCM and Hoechst/PI staining showed that α-solanine could enhance the radiosensitivity of EC cells. α-Solanine could downregulate Survivin expression level by upregulating miR-138 expression in EC cells. Upregulation of miR-138 and knock down Survivin both enhanced the radiosensitivity of EC cells. Moreover, Survivin could restore the effect of α-solanine and miR-138 on radiosensitivity of EC cells.

Conclusions: α-solanine could enhance the radiosensitivity of esophageal cancer cells by inducing microRNA-138 expression, and probably be an effective radiosensitizer in treating EC.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Base Sequence
  • Binding Sites
  • Cell Count
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / radiation effects
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Comet Assay
  • Dose-Response Relationship, Drug
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Epithelial Cells / radiation effects
  • Esophagus / drug effects
  • Esophagus / metabolism
  • Esophagus / pathology
  • Esophagus / radiation effects
  • Gamma Rays
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Inhibitor of Apoptosis Proteins / antagonists & inhibitors
  • Inhibitor of Apoptosis Proteins / genetics
  • Inhibitor of Apoptosis Proteins / metabolism
  • MicroRNAs / agonists*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Radiation Tolerance / drug effects
  • Radiation Tolerance / genetics
  • Radiation-Sensitizing Agents / pharmacology*
  • Signal Transduction
  • Solanine / pharmacology*
  • Survivin

Substances

  • Antineoplastic Agents, Phytogenic
  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • MIRN138 microRNA, human
  • MicroRNAs
  • Radiation-Sensitizing Agents
  • Survivin
  • alpha-solanine
  • Solanine