Effect of low-frequency low-intensity ultrasound with microbubbles on prostate cancer hypoxia

Abstract

Angiogenesis plays an important role in tumor growth, invasiveness, and metastasis. It is well established that prostate cancer is exposed to fluctuating oxygen tensions and both acute and chronic hypoxia exist, and these conditions can upregulate angiogenesis-associated proteins such as hypoxia-inducible factor 1 alpha and vascular endothelial growth factor A. Low-frequency low-intensity ultrasound with microbubbles can induce obvious microvessel damage in tumors, cause cell necrosis or apoptosis. However, there is no information about whether the blocking blood effect of lowfrequency low-intensity ultrasound with microbubbles has an influence on hypoxia environment of prostate cancer. Therefore, we investigated the impact of different low-frequency low-intensity ultrasound with microbubbles radiation times on prostate tumors, observed the change in the hypoxia-inducible factor 1 alpha and vascular endothelial growth factor A protein levels, as well as cell proliferation, apoptosis, and tumor volume. The results indicated that as the radiation was repeated four times on each treatment day, the effects of interruption were durable, the cell proliferation was inhibited, and apoptosis was promoted, and the hypoxia-inducible factor 1 alpha and vascular endothelial growth factor A expression levels were lower in the treatment group than in the control group. When the radiation was carried out once per treatment day, the hypoxia response was stimulated, the hypoxia-inducible factor 1 alpha and vascular endothelial growth factor A expression levels were higher compared with the control group, and cell proliferation was promoted. In addition, the tumor volume increased obviously in the hypoxia-stimulated group, whereas tumors grew slowly in the hypoxia-suppressed group. The results of this work demonstrated that under the same conditions, different radiation times of low-frequency low-intensity ultrasound with microbubbles affect the hypoxia response differently, and the effect at least partly stimulates or inhibits tumor growth. KeywordsLow-frequency low-intensity ultrasound, prostate cancer, acute hypoxia, hypoxia-inducible factor 1 alpha, angiogenesis Date

Low‑intensity pulsed ultrasound promotes apoptosis and inhibits angiogenesis via p38 signaling‑mediated endoplasmic reticulum stress in human endothelial cells

“…These two cell lines are useful in vitro models for the study of endothelial functions, such as angiogenesis. Studies have reported that low-intensity ultrasound with microbubbles induces the evident microvascular damage in tumors, mainly due to inertial cavitation, which can cause cell necrosis or apoptosis (26,27). Acoustic cavitation can lead to mechanical damage of small blood vessels due to the expansion and collapse caused by oscillation of the microbubbles (28).…”

Advances in low-frequency ultrasound combined with microbubbles in targeted tumor therapy

“…It is reported that low-frequency ultrasound combined with microbubbles can promote apoptosis of prostate cancer cells, liver cancer cells, ovarian cancer cells, glioma cells, and human leukemia cells (Lagneaux et al, 2002;Bai et al, 2016;Gangeh et al, 2016), and reduce damage to normal tissues. Hou et al (2017) reported that low-frequency ultrasound combined with microbubbles can affect the hypoxic response of a tumor, inhibit tumor growth, and promote cell apoptosis. Shen YY et al (2017) reported that low-frequency ultrasound combined with microbubbles enhanced delivery of paclitaxel liposomes treating nude mice bearing intracranial glioblastoma xenografts.…”

Ultrasound-guided Microbubble in the Treatment of Cancer: A Mini Narrative Review

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