Dong Guogang, Jia Limin, Gao Shuhua, Lin Monan, Wang Ruilin, Yang Fuyu, Ruan Juanjuan, Lv Yanhong
Department of Anatomy, Harbin Medical University, Harbin 150086, China; Department of Radiology, The General Hospital of Eastern Theater Command of the Chinese People's Liberation Army (PLA), Nanjing 210002, China.
Department of Anatomy, Harbin Medical University, Harbin 150086, China.
J Photochem Photobiol B. 2024 Dec;261:113061. doi: 10.1016/j.jphotobiol.2024.113061. Epub 2024 Nov 6.
Sonodynamic therapy (SDT) is an innovative, non-invasive approach to cancer treatment, by using low-intensity ultrasound to trigger the activation of sonosensitizers localized within cancerous cells. This current study aimed to explore the therapeutic efficacy of a new sonosensitizer, Sinoporphyrin Sodium (DVDMS), under ultrasound irradiation, against oral squamous cell carcinoma (OSCC)-derived SCC-154 cells, both in vitro and in vivo.
Fluorescence spectra, cytotoxicity assessments, uptake mechanisms, and subcellular distributions of DVDMS within the SCC-154 cell line were detected. Additionally, the study comprehensively assessed the antitumor effect, oxidative stress responses, apoptosis, apoptosis-related proteins, autophagic processes, and ultrastructural changes in SCC-154 cells, both in vitro and in vivo, subsequent to treatment with low-intensity ultrasound (at 1.0 MHz, 1 W/cm in vitro and 3 W/cm in vivo) in conjunction with DVDMS also being examined.
The findings indicate that SCC-154 cells exhibit heightened sensitivity to DVDMS compared to SAS and HSC-3 cell lines. Within SCC-154 cells, DVDMS primarily localizes within the mitochondria and lysosomes. DVDMS-based SDT significantly increased the intracellular levels of reactive oxygen species (ROS), induced morphological changes such as mitochondrial swelling and formation of autolysosomes, and exhibited a notable dose-dependent reduction in cell viability in vitro. Also, DVDMS-SDT demonstrated significant inhibition of xenograft growth without discernible adverse effects. Mechanistically, DVDMS-SDT upregulated Bax expression while downregulating Bcl-2 expression, which led to the Bax/Bcl-2 ratio and induced autophagy.
DVDMS-SDT triggers mitochondrial-dependent apoptosis in SCC-154 cells, unlike 5-ALA and protoporphyrin IX (PpIX). Also, the combination of DVDMS with ultrasound stimulation induces autophagy, with the onset of autophagic processes preceding apoptosis.
声动力疗法（SDT）是一种创新的非侵入性癌症治疗方法，通过使用低强度超声触发癌细胞内定位的声敏剂的激活。本研究旨在探讨新型声敏剂锡卟啉钠（DVDMS）在超声照射下对口腔鳞状细胞癌（OSCC）来源的SCC - 154细胞的体内外治疗效果。
检测DVDMS在SCC - 154细胞系中的荧光光谱、细胞毒性评估、摄取机制和亚细胞分布。此外，该研究还全面评估了低强度超声（体外1.0 MHz，1 W/cm；体内3 W/cm）联合DVDMS处理后，SCC - 154细胞在体内外的抗肿瘤作用、氧化应激反应、凋亡、凋亡相关蛋白、自噬过程和超微结构变化。
研究结果表明，与SAS和HSC - 3细胞系相比，SCC - 154细胞对DVDMS表现出更高的敏感性。在SCC - 154细胞内，DVDMS主要定位于线粒体和溶酶体。基于DVDMS的声动力疗法显著增加了细胞内活性氧（ROS）水平，诱导了线粒体肿胀和自噬体形成等形态学变化，并在体外表现出明显的剂量依赖性细胞活力降低。此外，DVDMS - SDT对异种移植瘤生长具有显著抑制作用，且无明显不良反应。机制上，DVDMS - SDT上调Bax表达，同时下调Bcl - 2表达，导致Bax/Bcl - 2比值升高并诱导自噬。
与5 - 氨基乙酰丙酸和原卟啉IX（PpIX）不同，DVDMS - SDT触发SCC - 154细胞中线粒体依赖性凋亡。此外，DVDMS与超声刺激的联合诱导自噬，自噬过程先于凋亡发生。
