Sonoporation by low-frequency and low-power ultrasound enhances chemotherapeutic efficacy in prostate cancer cells in vitro

Abstract

Combination therapy is used to optimize anticancer efficacy and reduce the toxicity and side-effects of drugs upon systemic administration. Ultrasound (US) combined with micro-bubbles (UM) enhances the intracellular uptake of cytotoxic drugs by tumor cells, particularly drug-resistant cells. In the present study, low-frequency and low-energy US (US irradiation conditions: frequency, 21 kHz; power density, 0.113 W/cm2; exposure time, 2 min at a duty cycle of 70%; and valid treatment time, 84 sec) were used in combination with microbubbles (100 μl/ml) to deliver mitoxantrone HCl (MIT) to DU145 cells. The results showed that UM did not change the cell viability in the short- or long-term. However, UM statistically enhanced the therapeutic effects and up to 31.26±3.34% of the cells exposed to UM were permeabilized compared with 9.74±2.55% of cells in the control, when using calcein (MW, 622.53) as a fluorogenic marker. Notably, UM affected the migration capability of the DU145 cells at 6 h post-treatment. In conclusion, the ultrasonic parameters used in the present study enhanced the chemotherapeutic effect and reduced the unwanted side-effects of MIT.

Low-frequency ultrasound-mediated microvessel disruption combined with docetaxel to treat prostate carcinoma xenografts in nude mice: A novel type of chemoembolization

“…However, a large percent of androgen-dependent cancers will gradually become resistant to castration, i.e., castration-resistant prostate cancer (CRPC) (2). At this stage, second-line endocrine therapy and chemotherapy should be administered (3). Docetaxel (DTX) is a clinically approved drug for the treatment of various metastatic CRPCs (4).…”

“…In addition, DTX has been reported to exert antiangiogenic effects (7). However, the systemic administration of DTX exposes all tissues to cytotoxic drugs (3). This side-effects of systemic chemotherapy highlights the requirement for improved and targeted delivery to aid in increased localized drug uptake in the targeted cancer cells.…”

“…As a highly effective, low-cost and non-invasive tool, low-frequency ultrasound combined with microbubbles (USMB) has the capacity of inducing drugs to accumulate in malignant tissues and reducing the toxic effects upon systemic administration to healthy tissues (3). Unlike in previous studies on USMB in combination with antitumor agents, which have largely focused on promoting uptake though enhancing permeability (3,8), the present study used USMB as an embolic 'agentʼ to retain chemotherapeutic drugs, in a similar manner to TACE.…”

“…Unlike in previous studies on USMB in combination with antitumor agents, which have largely focused on promoting uptake though enhancing permeability (3,8), the present study used USMB as an embolic 'agentʼ to retain chemotherapeutic drugs, in a similar manner to TACE. In theory, the mechanisms of chemoembolization using USMB include two aspects.…”

Upregulation of Beclin-1 expression in DU-145 cells following low-frequency ultrasound irradiation combined with microbubbles

“…Ultrasound has been widely used in cancer therapy and has been shown to mediate apoptosis through thermal, cavitation, sonoporation and sonochemical effects; however, the underlying mechanisms remain unclear (5). Furthermore, a number of experiments indicated that the effects of ultrasound may be enhanced by microbubbles (6,7).…”