Abstract：
Colorectal cancer (CRC) is significantly contributed to global cancer mortality rates. Treating CRC is particularly challenging due to metastasis and drug resistance. There is a pressing need for new treatment strategies against metastatic CRC. Photodynamic therapy (PDT) offers a well-established, minimally invasive treatment option for cancer with limited side effects. Hypericin (HYP), a potent photosensitizer for PDT, has been documented to induce cytotoxicity and apoptosis in various types of cancers. However, there are few reports on the inhibitory effects of HYP-mediated PDT on the metastatic ability of CRC cells. Here, we evaluate the inhibitory effects of HYP-mediated PDT against metastatic CRC cells and define its underlying mechanisms. Wound-healing and Transwell assays show that HYP-mediated PDT suppresses migration and invasion of CRC cells. F-actin visualization assays indicate HYP-mediated PDT decreases F-actin formation in CRC cells. TEM assays reveal HYP-mediated PDT disrupts pseudopodia formation of CRC cells. Mechanistically, immunofluorescence and western blotting results show that HYP-mediated PDT upregulates E-cadherin and downregulates N-cadherin and Vimentin. HYP-mediated PDT also suppresses key EMT regulators, including Snail, MMP9, ZEB1 and α-SMA. Additionally, the expressions of RhoA and ROCK1 are downregulated by HYP-mediated PDT. Together, these findings suggest that HYP-mediated PDT inhibits the migration and invasion of HCT116 and SW620 cells by modulating EMT and RhoA-ROCK1 signaling pathway. Thus, HYP-mediated PDT presents a potential therapeutic option for CRC.
摘要：
结直肠癌（CRC）是全球癌症死亡率的重要原因。由于转移和耐药性,治疗CRC特别具有挑战性。迫切需要针对转移性CRC的新治疗策略。光动力疗法（PDT）提供了一个完善的，癌症的微创治疗选择，副作用有限。金丝桃素(HYP),一种强效的PDT光敏剂，已被证明在各种类型的癌症中诱导细胞毒性和细胞凋亡。然而,关于HYP介导的PDT对CRC细胞转移能力的抑制作用的报道很少。这里,我们评估了HYP介导的PDT对转移性CRC细胞的抑制作用,并确定了其潜在机制.伤口愈合和Transwell测定显示HYP介导的PDT抑制CRC细胞的迁移和侵袭。F-肌动蛋白可视化测定表明HYP介导的PDT减少CRC细胞中的F-肌动蛋白形成。TEM测定揭示HYP介导的PDT破坏CRC细胞的伪足形成。机械上,免疫荧光和免疫印迹结果表明，HYP介导的PDT上调E-cadherin，下调N-cadherin和波形蛋白。HYP介导的PDT还抑制关键的EMT调节因子，包括蜗牛,MMP9、ZEB1和α-SMA。此外,HYP介导的PDT下调RhoA和ROCK1的表达。一起,这些发现表明HYP介导的PDT通过调节EMT和RhoA-ROCK1信号通路抑制HCT116和SW620细胞的迁移和侵袭。因此，HYP介导的PDT为CRC提供了潜在的治疗选择。
