Department of Oral and Maxillofacial Surgery II, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
Department of Dental and Oral Surgery, Izumisano Municipal Hospital, Izumisano, Osaka, Japan.
Cancer Gene Ther. 2015 Apr;22(3):163-8. doi: 10.1038/cgt.2015.3. Epub 2015 Feb 6.
Low-intensity ultrasound is a useful method to enhance the delivery of drugs to target cells via a range of mechanisms including the transient formation of micropores in the cell membrane, a process known as sonoporation. The effect of ultrasound on oncolytic herpes simplex virus type-1 (HSV-1) infection in oral squamous cell carcinoma (SCC) was examined. Human SCC cell line SAS and oncolytic HSV-1 RH2, which was deficient in the neurovirulent γ134.5 gene and exhibited cell fusion actions, were used. Cells grown in multi-well plates were infected with HSV-1 and exposed to ultrasound in the presence or absence of microbubbles after an adsorption period. The number of plaques was significantly greater than that of the untreated control. SAS cells were inoculated subcutaneously into nude mice and tumors were produced. Tumors were injected with HSV-1 RH2 with or without microbubbles and then exposed to ultrasound through the covering skin. The amount of the virus in tumor tissues 3 days after the injection was higher in tumors treated with HSV-1 RH2 and ultrasound than in tumors treated with RH2 only. The expression of the HSV-1 antigen was also increased by ultrasound and microbubbles. Tumor growth was suppressed with HSV-1 RH2 in combination with ultrasound, especially with microbubbles. These results indicated that ultrasound increased the efficiency of the HSV-1 infection in SAS cells and nude mouse tumors. This method can potentially be useful to enhance the antitumor effects of oncolytic HSV-1 on head and neck cancer treatment.
低强度超声是一种通过多种机制增强药物递送至靶细胞的有效方法，包括细胞膜中微孔的瞬时形成，该过程称为声孔作用。本研究探讨了超声对口腔鳞状细胞癌（SCC）中溶瘤单纯疱疹病毒 1 型（HSV-1）感染的影响。使用人 SCC 细胞系 SAS 和缺乏神经毒性 γ134.5 基因并具有细胞融合作用的溶瘤 HSV-1 RH2。在吸附期后，将在多孔板中生长的细胞用 HSV-1 感染，并在存在或不存在微泡的情况下进行超声处理。与未处理的对照组相比，噬菌斑的数量明显更多。将 SAS 细胞皮下接种到裸鼠中以产生肿瘤。用 HSV-1 RH2 处理肿瘤，无论是否有微泡，然后通过覆盖的皮肤进行超声处理。与单独用 RH2 处理的肿瘤相比，注射后 3 天肿瘤组织中的病毒量在接受 HSV-1 RH2 和超声处理的肿瘤中更高。超声和微泡还增加了 HSV-1 抗原的表达。与单独用 HSV-1 RH2 处理相比，联合使用 HSV-1 RH2 和超声，特别是联合使用微泡，可抑制肿瘤生长。这些结果表明，超声可提高 HSV-1 在 SAS 细胞和裸鼠肿瘤中的感染效率。该方法可能有助于增强溶瘤单纯疱疹病毒 1 对头颈部癌症治疗的抗肿瘤作用。
