Overcoming breast cancer cell treatment resistance by optimizing sonodynamic therapy and radiation sensitizers on lncRNA PVT1 and miR-1204 expression
Ali Neshasteh‐Riz, Zeinab Hormozi-Moghaddam, Zahra Abedi Kichi, Seyedeh Mona Taheri, Seyed Mohammad Amini, Amir Aghaei
Abstract
• An optimal sonodynamic effect in vitro was achieved with the combination of nanoparticles, methylene blue, ionizing radiation, and ultrasound on MCF7 cell line. • This combination protocol also resulted in an optimal level of ROS formation. • The expression of miR-1204 and lncRNA PVT1, which influence the DNA damage response pathway and the p53 activation pathway, was altered in MCF7 cancer cells treated with this combination method. 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. 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. Sonodynamic therapy at a mechanical index of 0.31 as acoustic cavitation threshold increased intracellular ROS. Combining sonodynamic therapy and 2Gy 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 20576.2 ± 4.6 (>4.5 times). The combined treatment also increased p53 expression and decreased the expression of PVT1, miR-1204, and related genes. 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.