Inflammation plays a key role in tumor promotion and development. Indeed, cyclooxygenase-2 (COX-2) expression is strongly associated with different types of cancer. An emerging class of compounds with significant anti-inflammatory properties is the hydrogen sulfide-releasing non-steroidal anti-inflammatory drugs (H₂S-NSAIDs). They consist of a traditional NSAID to which an H₂S-releasing moiety is covalently attached. We have recently demonstrated that H₂S donors inhibit melanoma cell proliferation. In the current study, we evaluated the potential beneficial effects of a new H₂S-releasing derivative of naproxen, ATB-346 [2-(6-methoxynapthalen-2-yl)-propionic acid 4-thiocarbamoyl phenyl ester] which inhibits COX activity but also releases H₂S.

We used cell culture and a mouse melanoma model to evaluate the effect of ATB-346 on: i) in vitro growth of human melanoma cells; ii) in vivo melanoma development in mice.

Cell culture studies demonstrated that ATB-346 reduced the in vitro proliferation of human melanoma cells and this effect was associated to induction of apoptosis and inhibition of NF-κB activation. Moreover, ATB-346 had novel Akt signaling inhibitory properties. Daily oral dosing of ATB-346 (43 μmol/kg) significantly reduced melanoma development in vivo.

This study shows that ATB-346, a novel H₂S-NSAID, inhibits human melanoma cell proliferation by inhibiting pro-survival pathways associated with NF-κB and Akt activation. Furthermore, oral treatment with ATB-346 inhibits melanoma growth in mice. In conclusion, the combination of inhibition of cyclooxygenase and delivery of H₂S by ATB-346 may offer a promising alternative to existing therapies for melanoma.

炎症在肿瘤的促进和发展中起关键作用。实际上，环氧合酶2（COX-2）的表达与不同类型的癌症密切相关。具有显着抗炎特性的一类新兴化合物是释放硫化氢的非甾体抗炎药（H ₂ S-NSAIDs）。它们由传统的NSAID组成，H ₂ S释放基团与之共价连接。我们最近证明，H ₂ S供体抑制黑素瘤细胞增殖。在当前的研究中，我们评估了新型H ₂的潜在有益作用S-释放衍生物萘普生，ATB-346 [2-（6- methoxynapthalen -2-基） -丙酸4-硫代氨基甲酰基苯基酯]，其抑制COX活性，而且释放ħ ₂ S.

我们使用细胞培养和小鼠黑素瘤模型来评估ATB-346对以下方面的作用：i）人黑素瘤细胞的体外生长；ii）小鼠体内黑色素瘤的发展。

细胞培养研究表明，ATB-346减少了人黑素瘤细胞的体外增殖，这种作用与诱导细胞凋亡和抑制NF-κB活化有关。此外，ATB-346具有新颖的Akt信号抑制特性。每日口服ATB-346（43μmol/ kg）可显着减少体内黑色素瘤的发生。

这项研究表明，新型H ₂ S-NSAID ATB-346通过抑制与NF-κB和Akt激活相关的生存途径来抑制人黑素瘤细胞增殖。此外，用ATB-346口服治疗可抑制小鼠黑色素瘤的生长。总之，ATB-346抑制环加氧酶和递送H ₂ S的组合可能为现有的黑色素瘤治疗方法提供有希望的替代方法。