Comparison of hypocrellin B-mediated sonodynamic responsiveness between sensitive and multidrug-resistant human gastric cancer cell lines

J Med Ultrason (2001). 2019 Jan;46(1):15-26. doi: 10.1007/s10396-018-0899-5. Epub 2018 Oct 11.

Abstract

Objectives: The aim of this study was to compare the different responses to hypocrellin B (HB)-mediated sonodynamic treatment between human gastric adenocarcinoma cell line SGC7901 and SGC7901/ADR.

Methods: Tumor cells in culture dishes (35-mm diameter) were exposed to planar ultrasound at an intensity of 0.5 W/cm2 for 60 s combined with/without 2.5 μM HB. Cell viability was determined by MTT and Guava ViaCount assay. Production of reactive oxygen species (ROS) and destabilization of the mitochondrial membrane potential were assessed by flow cytometry. Apoptosis was analyzed using annexin-PE/7-amino-actinomycin D staining. The cell membrane integrity was estimated by isothiocyanate-dextran (FD500) uptake assay. Ultrastructural alterations on the membrane surface were observed by scanning electron microscopy. The membrane fluidity was also compared between the two cell lines using spectrophotometry.

Results: Compared with SGC7901 cells, HB-mediated sonodynamic therapy (HB-SDT) showed higher cytotoxic in SGC7901/ADR cells at the same treatment doses. Abundant intracellular ROS, a decrease in the mitochondrial membrane potential, and an increased rate of apoptosis were detected in the SDT group of both cell lines, wherein SGC7901/ADR cells showed a much more higher rate. Cell membrane permeability was remarkably enhanced after HB-SDT application. In addition, relatively severe cell damage was observed under scanning electron microscopy after HB-SDT treatment in SGC7901/ADR cells compared with SGC7901 cells.

Conclusions: These results suggest that HB-SDT could induce apoptosis in SGC7901 and SGC7901/ADR cells via production of ROS. SGC7901/ADR was found to be more sensitive to HB-SDT than SGC7901 cells under the same experimental condition. Meanwhile, a noteworthy difference in cell membrane injury between SGC7901 and SGC7901/ADR cells was detected. The decreased membrane fluidity in SGC7901/ADR cells may be one of the reasons for its increased membrane damage.

Keywords: Gastric cancer; Hypocrellin B; Multidrug-resistant; Sonodynamic therapy.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adenocarcinoma / therapy*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Humans
  • Perylene / analogs & derivatives*
  • Perylene / pharmacology
  • Quinones / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / therapy*
  • Tumor Cells, Cultured
  • Ultrasonic Therapy / methods*

Substances

  • Quinones
  • Reactive Oxygen Species
  • Perylene
  • hypocrellin B