Overcoming breast cancer cell treatment resistance by optimizing sonodynamic therapy and radiation sensitizers on lncRNA PVT1 and miR-1204 expression

Background

Acoustic cavitation is a foundational mechanism in ultrasound therapy, primarily through inertial cavitation resulting from microbubble collapse. Sonodynamic therapy, with inertial acoustic cavitation threshold and low-dose radiation in the presence of sensitizers, may provide significant effects for cancer treatment, potentially overcoming resistance encountered with single therapies.

Methods

MCF7 breast cancer cells were subjected to sonodynamic therapy either alone or combined with ionizing radiation, gold nanoparticles coated with apigenin, and methylene blue. Several parameters were evaluated, including reactive oxygen species (ROS) generation and colonization. Additionally, the investigation included assessing the long non-coding RNA (lncRNA) PTV1 with miRNA1204 and related genes using Real-Time PCR.

Results

Sonodynamic therapy at a mechanical index of 0.31 as acoustic cavitation threshold increased intracellular ROS. Combining sonodynamic therapy and 2 Gy X-ray radiation with methylene blue and gold nanoparticles coated with apigenin significantly decreased plating efficiency (4.44±1.69), and survival fraction (2.75±1.98) compared with control (Ctrl.) (98.77±4.49) and (97.59± 2.94), respectively. This was associated with a marked increase in ROS with a mean fluorescence intensity of 20,576.2 ± 4.6 (>4.5 times). The combined treatment also increased p53 expression and decreased the expression of PVT1, miR-1204, and related genes.

Conclusion

Sonodynamic therapy in inertial acoustic cavitation threshold, combined with ionizing radiation in the presence of biocompatible nanoparticles, could enhance the therapeutic effects on the miR-1204, derived from lncRNA PVT1, that functions as an oncogenic microRNA in breast cancer. This approach has the potential to overcome treatment resistance encountered with single therapies.