Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, Shanghai Fengxian District Central Hospital, Shanghai, People's Republic of China.
Department of Neurosurgery, The Fourth College Hospital of Harbin Medical University, Harbin, People's Republic of China.
Onco Targets Ther. 2014 Sep 30;7:1801-10. doi: 10.2147/OTT.S52426. eCollection 2014.
The study reported here examined the effect of hematoporphyrin monomethyl ether (HMME)-mediated sonodynamic therapy (SDT) on C6 gliomas implanted in rat brains.
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/cm(2).
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.
This study with a rat C6 glioma experimental model showed that SDT can potentially be useful in the treatment of deep-seated malignant gliomas.
本研究探讨了血卟啉单甲醚（HMME）介导的声动力学疗法（SDT）对植入大鼠脑内的 C6 神经胶质瘤的影响。
接种后 2 周，通过 1.5 T 磁共振成像仪测量肿瘤体积来评估神经胶质瘤的发展情况。当肿瘤直径达到 3-5 毫米时，将具有发达 C6 神经胶质瘤的大鼠用于测试 SDT、超声单独治疗和 HMME 单独治疗。对给予和未给予静脉注射 10μg/mL HMME 的大鼠，用 1 MHz 超声以 0.5 W/cm2 的剂量进行照射。
SDT 治疗可有效抑制颅内神经胶质瘤的生长。单独使用超声治疗可在 1 周内抑制神经胶质瘤的生长；然而，1 周后，肿瘤开始再次生长。相比之下，SDT 的作用可持续至少 2 周。单独注射 HMME 对抑制神经胶质瘤的生长没有影响，这表明声敏剂 HMME 没有抗肿瘤作用。SDT 和超声单独治疗均可延长植入 C6 神经胶质瘤大鼠的存活时间。病理和电子显微镜检查表明，SDT 和超声单独治疗可通过触发神经胶质瘤细胞凋亡来诱导神经胶质瘤坏死，这通过用细胞色素 c 和 caspase-3 抗体进行免疫组化检查得到证实。最重要的是，我们发现声敏剂 HMME 可以通过选择性辅助超声靶向抑制神经胶质瘤血管生成来增强超声诱导的抗肿瘤作用。
本研究采用大鼠 C6 神经胶质瘤实验模型表明，SDT 可能对治疗深部恶性神经胶质瘤有用。
