Skip to main content
Log in

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

  • Original Article
  • Published:
Journal of Medical Ultrasonics Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Hartgrink HH, Jansen EP, van Grieken NC, et al. Gastric cancer. Lancet. 2009;374:477–90.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Mu J, Liu T, Jiang L, et al. The traditional chinese medicine baicalein potently inhibits gastric cancer cells. J Cancer. 2016;7:453–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Parkin DM, Pisani P, Ferlay MJ. Global cancer statistics. CA Cancer J Clin. 1999;49:33–64.

    Article  CAS  PubMed  Google Scholar 

  4. Wang P, Li Z, Liu H, et al. MicroRNA-126 increases chemosensitivity in drug-resistant gastric cancer cells by targeting EZH2. Biochem Biophys Res Commun. 2016;479:91–6.

    Article  CAS  PubMed  Google Scholar 

  5. Sun W, Lv C, Zhu T, et al. Ophiobolin-O reverses adriamycin resistance via cell cycle arrest and apoptosis sensitization in adriamycin-resistant human breast carcinoma (MCF-7/ADR) cells. Mar Drugs. 2013;11:4570–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Li C, Zhang K, Wang P, et al. Sonodynamic antitumor effect of a novel sonosensitizer on S180 solid tumor. Biopharm Drug Dispos. 2014;35:50–9.

    Article  CAS  PubMed  Google Scholar 

  7. Li Q, Wang X, Wang P, et al. Efficacy of chlorin e6-mediated sono-photodynamic therapy on 4T1 cells. Cancer Biother Radiopharm. 2014;29:42–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Li Y, Wang P, Wang X, et al. Involvement of mitochondrial and reactive oxygen species in the sonodynamic toxicity of chlorin e6 in human leukemia K562 cells. Ultrasound Med Biol. 2014;40:990–1000.

    Article  PubMed  Google Scholar 

  9. Jia Y, Yuan W, Zhang K, et al. Comparison of cell membrane damage induced by the therapeutic ultrasound on human breast cancer MCF-7 and MCF-7/ADR cells. Ultrason Sonochem. 2015;26:128–35.

    Article  CAS  PubMed  Google Scholar 

  10. Su X, Chen Y, Wang X, et al. PpIX induces mitochondria-related apoptosis in murine leukemia L1210 cells. Drug Chem Toxicol. 2014;37:348–56.

    Article  CAS  PubMed  Google Scholar 

  11. Wang H, Wang X, Wang P, et al. Ultrasound enhances the efficacy of chlorin E6-mediated photodynamic therapy in MDA-MB-231 cells. Ultrasound Med Biol. 2013;39:1713–24.

    Article  PubMed  Google Scholar 

  12. Shen S, Wu L, Liu J, et al. Core-shell structured Fe3O4@TiO2-doxorubicin nanoparticles for targeted chemo-sonodynamic therapy of cancer. Int J Pharm. 2015;486:380–8.

    Article  CAS  PubMed  Google Scholar 

  13. Wang H, Wang P, Li L, et al. Microbubbles enhance the antitumor effects of sinoporphyrin sodium mediated sonodynamic therapy both in vitro and in vivo. Int J Biol Sci. 2015;11:1401–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Yoshida T, Kondo T, Ogawa R, et al. Combination of doxorubicin and low-intensity ultrasound causes a synergistic enhancement in cell killing and an additive enhancement in apoptosis induction in human lymphoma U937 cells. Cancer Chemother Pharmacol. 2008;61:559–67.

    Article  CAS  PubMed  Google Scholar 

  15. Jiang Y, Leung AW, Wang X, et al. Effect of photodynamic therapy with hypocrellin B on apoptosis, adhesion, and migration of cancer cells. Int J Radiat Biol. 2014;90:575–9.

    Article  CAS  PubMed  Google Scholar 

  16. Jiang Y, Xia X, Leung AW, et al. Apoptosis of breast cancer cells induced by hypocrellin B under light-emitting diode irradiation. Photodiagnosis Photodyn Ther. 2012;9:337–43.

    Article  CAS  PubMed  Google Scholar 

  17. Jiang Y, Leung AW, Wang X, et al. Inactivation of Staphylococcus aureusby photodynamic action of hypocrellin B. Photodiagnosis Photodyn Ther. 2013;10:600–6.

    Article  CAS  PubMed  Google Scholar 

  18. Wang P, Xu CS, Xu J, et al. Hypocrellin B enhances ultrasound-induced cell death of nasopharyngeal carcinoma cells. Ultrasound Med Biol. 2010;36:336–42.

    Article  PubMed  Google Scholar 

  19. Wang X, Leung AW, Jiang Y, et al. Hypocrellin B-mediated sonodynamic action induces apoptosis of hepatocellular carcinoma cells. Ultrasonics. 2012;52:543–6.

    Article  CAS  PubMed  Google Scholar 

  20. Wang X, Ip M, Leung AW, et al. Sonodynamic action of hypocrellin B on methicillin-resistant Staphylococcus aureus. Ultrasonics. 2016;65:137–44.

    Article  CAS  PubMed  Google Scholar 

  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.

    PubMed  PubMed Central  Google Scholar 

  22. Wang X, Hu J, Zhang S, et al. Analysis of the in vivo and in vitro effects of photodynamic therapy on breast cancer by using a sensitizer, sinoporphyrin sodium. Theranostics. 2015;7:772–86.

    Article  CAS  Google Scholar 

  23. Wang ZB, Liu YQ, Zhang Y, et al. Reactive oxygen species, but not mitochondrial membrane potential, is associated with radiation-induced apoptosis of AHH-1 human lymphoblastoid cells. Cell Biol Int. 2007;31:1353–8.

    Article  CAS  PubMed  Google Scholar 

  24. Wang X, Leung AW, Hua H, et al. Sonodynamic action of hypocrellin B on biofilm-producing Staphylococcus epidermidis in planktonic condition. J Acoust Soc Am. 2015;138:2548–53.

    Article  PubMed  Google Scholar 

  25. Krishna R, Mayer LD. Multidrug resistance (MDR) in cancer. Mechanisms, reversal using modulators of MDR and the role of MDR modulators in influencing the pharmacokinetics of anticancer drugs. Eur J Pharm Sci. 2000;11:265–83.

    Article  CAS  PubMed  Google Scholar 

  26. Wang H, Wang X, Zhang S, et al. Sinoporphyrin sodium, a novel sensitizer, triggers mitochondrial-dependent apoptosis in ECA-109 cells via production of reactive oxygen species. Int J Nanomed. 2014;2014:3077–90.

    Article  CAS  Google Scholar 

  27. Escoffre JM, Piron J, Novell A, et al. Doxorubicin delivery into tumor cells with ultrasound and microbubbles. Mol Pharm. 2011;8:799–806.

    Article  CAS  PubMed  Google Scholar 

  28. Tang W, Fan W, Liu Q, et al. The role of p53 in the response of tumor cells to sonodynamic therapy in vitro. Ultrasonics. 2011;51:777–85.

    Article  CAS  PubMed  Google Scholar 

  29. Costley D, Mc Ewan C, Fowley C, et al. Treating cancer with sonodynamic therapy: a review. Int J Hyperthermia. 2015;31:107–17.

    Article  CAS  PubMed  Google Scholar 

  30. Zheng X, Wu J, Shao Q, et al. Apoptosis of THP-1 macrophages induced by pseudohypericin-mediated sonodynamic therapy through the mitochondria-caspase pathway. Cell Physiol Biochem. 2016;38:545–57.

    Article  CAS  PubMed  Google Scholar 

  31. Yumita N, Iwase Y, Nishi K, et al. Involvement of reactive oxygen species in sonodynamically induced apoptosis using a novel porphyrin derivative. Theranostics. 2012;2:880–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Li Q, Liu Q, Wang P, et al. The effects of Ce6-mediated sono-photodynamic therapy on cell migration, apoptosis and autophagy in mouse mammary 4T1 cell line. Ultrasonics. 2014;54:981–9.

    Article  CAS  PubMed  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.

    CAS  Google Scholar 

  34. Miller DL, Dou C. Membrane damage thresholds for pulsed or continuous ultrasound in phagocytic cells loaded with contrast agent gas bodies. Ultrasound Med Biol. 2004;30:405–11.

    Article  PubMed  Google Scholar 

  35. Hao Q, Liu Q, Wang X, et al. Membrane damage effect of therapeutic ultrasound on Ehrlich ascitic tumor cells. Cancer Biother Radiopharm. 2009;24:41–8.

    Article  CAS  PubMed  Google Scholar 

  36. Yang L, Wei DD, Chen Z, et al. Reversal of multidrug resistance in human breast cancer cells by Curcuma wenyujin and Chrysanthemum indicum. Phytomedicine. 2011;18:710–8.

    Article  CAS  PubMed  Google Scholar 

  37. Boutin C, Roche Y, Millot C, et al. High heterogeneity of plasma membrane microfluidity in multidrug-resistant cancer cells. J Biomed Opt. 2009;14:034030.

    Article  CAS  PubMed  Google Scholar 

  38. Hassan MA, Furusawa Y, Minemura M, et al. Ultrasound-induced new cellular mechanism involved in drug resistance. PLoS One. 2012;7:e48291.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Wang E, Lee MD, Dunn KW. Lysosomal accumulation of drugs in drug-sensitive MES-SA but not multidrug-resistant MES-SA/Dx5 uterine sarcoma cells. J Cell Physiol. 2000;184:263–74.

    Article  CAS  PubMed  Google Scholar 

  40. Tang W, Liu Q, Wang X, et al. Membrane fluidity altering and enzyme inactivating in sarcoma 180 cells post the exposure to sonoactivated hematoporphyrin in vitro. Ultrasonics. 2008;48:66–73.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

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).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Pan Wang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical statements

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.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, Y., Bai, H., Wang, H. et al. Comparison of hypocrellin B-mediated sonodynamic responsiveness between sensitive and multidrug-resistant human gastric cancer cell lines. J Med Ultrasonics 46, 15–26 (2019). https://doi.org/10.1007/s10396-018-0899-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10396-018-0899-5

Keywords

Navigation