Comparison of hypocrellin B-mediated sonodynamic responsiveness between sensitive and multidrug-resistant human gastric cancer cell lines
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.
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.
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.
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.
KeywordsSonodynamic therapy Hypocrellin B Multidrug-resistant Gastric cancer
This work was supported by the National Natural Science Foundation of China (Grant No. 81872497), the Fundamental Research Funds for the Central Universities (No. GK201602003, 2016TS056), and the Natural Science Foundation of Shaanxi Province (No. 2017JM8004).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions.
- 21.Bai M, Shen M, Teng Y, et al. Enhanced therapeutic effect of Adriamycin on multidrug resistant breast cancer by the ABCG2-siRNA loaded polymeric nanoparticles assisted with ultrasound. Oncotarget. 2015;6:43779–90.Google Scholar
- 33.Wang X, Luo J, Leung AW, et al. Hypocrellin B in hepatocellular carcinoma cells: subcellular localization and sonodynamic damage. Int J Radiat Biol. 2015;91:1–22.Google Scholar