一种基于叶绿素 e6 衍生物的光动力疗法通过 Akt/mTOR 信号通路抑制皮肤鳞状细胞癌细胞增殖。
A chlorin e6 derivative-mediated photodynamic therapy inhibits cutaneous squamous cell carcinoma cell proliferation via Akt/mTOR signaling pathway.
机构信息
Shanghai Skin Disease Clinical College of Anhui Medical University, Shanghai, 200443, China; Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China; The Fifth Clinical Medical College of Anhui Medical University.
Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China.
出版信息
Photodiagnosis Photodyn Ther. 2023 Jun;42:103332. doi: 10.1016/j.pdpdt.2023.103332. Epub 2023 Feb 14.
BACKGROUND AND OBJECTIVES
Although most cutaneous squamous cell carcinoma (cSCC) cases are generally nonlethal and manageable with surgical excision, there ares till significant hazards for patients who are ineligible for surgical resection. We sought to find a suitable and effective treatment for cSCC.
METHODS
We modified chlorin e6 by adding a hydrogen chain with a six-carbon ring to the benzene ring and named this new photosensitizer as STBF. We first investigated the fluorescence characteristics, cellular uptake of STBF and subcellular localization. Next, cell viability was detected by CCK-8 assay and the TUNEL staining was performed. Akt/mTOR-related proteins were examined by western blot.
RESULTS
STBF-photodynamic therapy (PDT) inhibits cSCC cells viability in a light dose dependent manner. The antitumor mechanism of STBF-PDT might be due to the suppression of the Akt/mTOR signaling pathway. Further animal investigation determined that STBF-PDT led to a marked reduction in tumor growth.
CONCLUSIONS
Our results suggest that STBF-PDT exerts significant therapeutic effects in cSCC. Thus, STBF-PDT is expected to be a promising method for the treatment of cSCC and the photosensitizer STBF may be destined for a wider range of applications in photodynamic therapy.
背景与目的
虽然大多数皮肤鳞状细胞癌（cSCC）病例通常是非致命的，并且可以通过手术切除来控制，但对于不符合手术切除条件的患者，仍存在重大风险。我们试图寻找一种适合且有效的治疗 cSCC 的方法。
方法
我们通过在苯环上添加一个具有六碳环的氢链来修饰叶绿素 e6，并将这种新的光敏剂命名为 STBF。我们首先研究了 STBF 的荧光特性、细胞摄取和亚细胞定位。接下来，通过 CCK-8 检测法检测细胞活力，并进行 TUNEL 染色。通过 Western blot 检测 Akt/mTOR 相关蛋白。
结果
STBF-光动力疗法（PDT）以光剂量依赖性方式抑制 cSCC 细胞活力。STBF-PDT 的抗肿瘤机制可能是由于抑制了 Akt/mTOR 信号通路。进一步的动物研究表明，STBF-PDT 导致肿瘤生长明显减少。
结论
我们的结果表明，STBF-PDT 在 cSCC 中具有显著的治疗效果。因此，STBF-PDT 有望成为治疗 cSCC 的一种有前途的方法，而光敏剂 STBF 可能在光动力疗法中有更广泛的应用前景。
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