Study of the mechanism of sonodynamic therapy in a rat glioma model
Dayong Song,1 Wu Yue,2 Zhiqiang Li,1 Jianhua Li,2 Jun Zhao,1 Ning Zhang1
1Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, Shanghai Fengxian District Central Hospital, Shanghai, 2Department of Neurosurgery, The Fourth College Hospital of Harbin Medical University, Harbin, People's Republic of China
Purpose: The study reported here examined the effect of hematoporphyrin monomethyl ether (HMME)-mediated sonodynamic therapy (SDT) on C6 gliomas implanted in rat brains.
Methods: Two weeks after inoculation, glioma development was evaluated by measuring tumor volume using a 1.5 T magnetic resonance imager. Rats that had a well-developed C6 glioma (usually when the tumor diameter reached 3–5 mm) were used to test SDT, ultrasound-alone, and HMME-alone treatments. Rats both administered and not administered intravenous HMME 10 µg/mL were insonated by a 1 MHz ultrasound at a dose of 0.5 W/cm2.
Results: SDT treatment could effectively inhibit the expansion of intracranial gliomas in vivo. The treatment with ultrasound alone could inhibit glioma growth within 1 week; however, 1 week later, the tumor started growing again. In contrast, the effect of SDT could last at least 2 weeks. Injection of HMME alone had no effects on inhibiting glioma growth, suggesting the sonosensitizer HMME has no antitumor effect. Both SDT and ultrasound-alone treatment could extend the survival of rats implanted with a C6 glioma. Pathological and electron microscopic examinations suggested SDT and ultrasound-alone treatment could induce glioma necrosis by way of triggering glioma-cell apoptosis, which was confirmed by immunohistological examination with cytochrome-c and caspase-3 antibodies. Most importantly, we found that the sonosensitizer HMME could enhance the ultrasound-induced antitumor effect by selectively assisting ultrasound targeting of glioma angiogenesis inhibition.
Conclusion: This study with a rat C6 glioma experimental model showed that SDT can potentially be useful in the treatment of deep-seated malignant gliomas.
Keywords: antitumor mechanism, ultrasound, hematoporphyrin monomethyl ether
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