背景:黑色素瘤是一种高侵袭性皮肤癌,治疗策略有限。布比卡因,一种因其安全性而公认的常用局部麻醉药,在对抗肿瘤方面表现出了希望。3'-磷酸腺苷5'-磷酸硫酸合酶2(PAPSS2)是硫酸化过程中的关键酶,与各种肿瘤的发展和转移有关。本研究旨在探讨布比卡因通过靶向PAPSS2抑制黑色素瘤增殖和转移的机制。
方法:使用细胞计数试剂盒-8(CCK-8)评估布比卡因对A375和A2058黑色素瘤细胞增殖的影响,5-乙炔基-2'-脱氧尿苷(EdU)标记,和克隆检测。细胞迁移,入侵,使用Transwell实验和定量逆转录聚合酶链反应(qRT-PCR)分析评估PAPSS2表达。此外,在裸鼠体内构建黑色素瘤肿瘤模型,以评估布比卡因对黑色素瘤生长和转移的影响.免疫组织化学用于评估裸鼠模型中的肿瘤转移和PAPSS2表达水平。
结果:实验结果表明,与对照组相比,布比卡因显著抑制黑素瘤增殖和侵袭。值得注意的是,PAPSS2过表达部分逆转了这种抑制作用。体内实验表明,布比卡因处理的裸鼠表现出减少的肿瘤体积,重量,肺转移灶较少。通过qRT-PCR和免疫组织化学分析的分子分析进一步表明布比卡因显著降低肿瘤组织中的PAPSS2。
结论:这项研究证实了布比卡因,局部麻醉剂,可以通过靶向PAPSS2信号通路抑制黑色素瘤的增殖和转移。这些发现表明其作为抗肿瘤药物的潜力,并提出了黑色素瘤的新治疗策略。
BACKGROUND: Melanoma is a highly invasive skin cancer with limited treatment strategies. Bupivacaine, a commonly used local anesthetic recognized for its safety, has shown promise in combating tumors. 3\'-phosphoadenosine 5\'-phosphosulfate synthase 2 (
PAPSS2) is a key enzyme in the sulfation process and is associated with the development and metastasis of various tumors. This study aimed to explore the mechanism by which bupivacaine inhibits melanoma proliferation and metastasis by targeting
PAPSS2.
METHODS: The effects of bupivacaine on the proliferation of A375 and A2058 melanoma cells were evaluated using Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2\'-deoxyuridine (EdU) labeling, and clonogenic assays. Cell migration, invasion, and
PAPSS2 expression were evaluated using Transwell experiments and Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) analysis. Additionally, an in vivo melanoma tumor model in nude mice was constructed to evaluate the impact of bupivacaine on melanoma growth and metastasis. Immunohistochemistry was used to assess tumor metastasis and
PAPSS2 expression levels in the nude mouse model.
RESULTS: Experimental results demonstrated that bupivacaine significantly inhibited melanoma proliferation and invasion compared to the control group. Notably, this inhibitory effect was partially reversed by
PAPSS2 overexpression. In vivo experiments demonstrated that bupivacaine-treated nude mice exhibited reduced tumor volumes, weights, and fewer lung metastatic foci. Molecular analysis via qRT-PCR and immunohistochemistry analysis further indicated that bupivacaine significantly reduced PAPSS2 in tumor tissues.
CONCLUSIONS: This study confirms that bupivacaine, a local anesthetic, can inhibit melanoma proliferation and metastasis by targeting the PAPSS2 signaling pathway. These findings suggest its potential as an anti-tumor medication and present new treatment strategies for melanoma.