Low-frequency ultrasound irradiation increases paclitaxel-induced sarcoma cells apoptosis and facilitates the transmembrane delivery of drugs

Abstract

Sarcoma is a malignant tumor derived from interstitial tissues and requires comprehensive treatment including chemotherapy. Paclitaxel (PTX) is an active agent against sarcoma, but its effect is not sufficiently acceptable and needs to be improved. Low-frequency ultrasound (LFU) has been documented to improve the efficacy of drugs by inducing reversible changes in membrane permeability; however, the effects of the combined use of LFU and PTX for sarcoma tumors remain unclear and warrant further investigation. We investigated the effects of 30 kHz LFU treatment combined with PTX on sarcoma cells A-204 and HT-1080 by analyzing in vitro apoptosis and cell growth inhibition rates, and determined their antitumor effects by examining tumor weights with or without LFU in the S180 sarcoma xenograft model. Drug concentrations in the subcutaneous tumors were measured using high performance liquid chromatography (HPLC). LFU combined with PTX significantly induced cell apoptosis, and blocked the cell cycle of sarcoma cells in G2/M phase, and furthermore, inhibited the activation of JAK2/STAT3 signaling pathway. Meanwhile, LFU combined with PTX inhibited the expression of PD-L1 in vitro, suggesting the potential of enhanced antitumor immunity by this treatment. LFU combined with PTX significantly inhibited the growth of S180 tumors transplanted subcutaneously in Institute of Cancer Research (ICR) mice, and its enhanced effect may be associated with increased local concentrations of PTX in tumor tissues in vivo, with no significant adverse subsequences on body weight observed. We conclude that the combination of LFU and PTX has synergistic antitumor effects and is a candidate for subcutaneous treatment of sarcoma by further increasing the intracellular concentration of PTX.

In Vitro Studies of Pegylated Magnetite Nanoparticles in a Cellular Model of Viral Oncogenesis: Initial Studies to Evaluate Their Potential as a Future Theranostic Tool

“…One strategy is focus on the development of paclitaxel nanocrystal formulation to improve the water solubility properties of this hydrophobic drug [ 42 ]. In another case, low-frequency ultrasound irradiation was used to improve the efficacy of paclitaxel to induce apoptosis of sarcoma cells [ 43 ]. Another strategy for solid tumor treatment has emerged using a novel extracellular matrix (ECM)-targeting nanotherapeutic.…”

Ultrasound combined with microbubble mediated immunotherapy for tumor microenvironment

“…Studies have shown that under the action of low-frequency ultrasound, the collapse process of MB caused by cavitation effect produces jets and releases energy, which can instantly rupture adjacent cell membrane, increase their permeability and promote the ingestion of drugs by cells ( Dong et al, 2017 ; Yang et al, 2018 ). At present, the way of using UTMD to improve the efficiency of drug targeting and delivery in local tissues is widely recognized in research ( Feril and Tachibana, 2012 ; Cai et al, 2022 ; Yang et al, 2022 ). Therefore, By combining ultrasound with microbubble therapy, tumor cells can be killed specifically, anti-tumor immune response can be stimulated, and tumor microenvironment can be improved, which is crucial for tumor immunotherapy ( Zhang et al, 2017 ).…”