Ultrasound-stimulated microbubbles enhances radiosensitivity in cervical cancer

Abstract

Background

Ultrasound-stimulated microbubble (USMB) therapy has proven efficacy of targeting tumor vasculature and enhancing the effect of radiation in tumor xenografts. In this investigation, we studied whether this treatment enhances the sensitivity of cervical cancer to radiation.

Methods

Human cervical cancer (ME-180 and SiHa) cells were treated with USMB or exposed to radiation (0, 2, 4, 6 and 8 Gy) or radiation (8 Gy) in combination with USMB. Clone formation assay and CCK-8 assay were used to analyze the proliferation capacity of cells. Apoptosis and DNA double-strand breaks were detected using flow cytometry and immunofluorescence staining of gamma-H2AX (γ-H2AX), respectively. Matrigel tubule formation was performed to evaluate the angiogenesis of human umbilical vein endothelial cells. In xenograft model of SiHa cells, tumor tissue expression of CD31 was detected by immunohistochemistry.

Results

USMB and radiation synergistically restrained the growth of ME-180 and SiHa cells. USMB promoted radiation-induced apoptosis by enhancing the levels of proapoptotic proteins. Furthermore, USMB enhanced radiation-induced γ-H2AX foci to induce DNA double-strand breaks in cervical cancer cells. USMB in combination with radiation reduced the angiogenic capacity of endothelial cells in vitro. Moreover, USMB strengthened the inhibitory effect of radiation on tumor growth and angiogenesis in xenograft models.

Conclusion

In conclusion, USMB exposure effectively enhanced the destructive effect of radiation on cervical cancer, suggesting that USMB might be a promising sensitizer of radiotherapy to treat cervical cancer.

Keywords:

• Cervical cancer
• ultrasound-stimulated microbubble
• radiotherapy
• vasculature

Acknowledgement

The authors appreciate all the participants providing supports for this study.

Authors’ contributions

Tianying Liu and Qing Xie were the main designers of this study. Tianying Liu, Qing Xie and Wenli Wang performed the experiments and analyzed the data. Tianying Liu, Qing Xie and Wenli Wang drafted the manuscript. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethical approval

Animal protocols were approved by the Institutional Animal Care and Use Committee of Hubei Provincial Center for Disease Control and Prevention (approval code: 202310059).

Data availability statement

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

None.

Notes on contributors

Tianying Liu

Tianying Liu graduated from Xi’an Jiaotong University with a bachelor’s degree in clinical medicine and is the deputy chief physician of Xidian Group Hospital, specializing in abdominal ultrasound, obstetrics and gynecology ultrasound, fetal malformation ultrasound screening, fetal heart ultrasound and superficial organ ultrasound diagnosis.

Qing Xie

Qing Xie graduated from Xi’an Jiaotong University with a master’s degree in medical imaging and is the chief physician of Third Hospital of Xi’an, Affiliated Hospital of Northwest University, specializing in difficult abdominal ultrasound, vascular ultrasound, obstetrics and gynecology ultrasound, fetal malformation ultrasound screening and fetal heart ultrasound.

Wenli Wang

Wenli Wang graduated from Xi’an Jiaotong University with a master’s degree in medical imaging and is the deputy chief physician of the Third Hospital of Xi’an, Affiliated Hospital of Northwest University, specializing in ultrasound screening of fetal malformation, ultrasound diagnosis of fetal heart and superficial organs, ultrasound-guided diagnosis of puncture.