Nickel compounds are known to be common environmental and occupational carcinogens which also promote the migration of lung cancer cells. However, the molecular mechanism yet remains to be clarified. Hydrogen sulfide (H₂S) is involved in cancer biological processes. However, the exact effect and functionality of H₂S on nickel, towards the promotion of the migration ability of lung cancer cells, remains to be unknown. In this study, we have found that the nickel chloride (NiCl₂) treatment significantly downregulates the protein levels of endogenous H₂S enzyme cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3-Mercaptopyruvate sulfurtransferase (3-MST). A correlation between NiCl₂-induced epithelial-mesenchymal transition (EMT) and the migration ability of lung cancer A549 cells has been observed. Exogenous H₂S donor, sodium hydrogen sulfide (NaHS) (100 μmol/L), can reverse NiCl₂-induced EMT as well as the migration ability of A549 cells. NiCl₂ treatment is able to upregulate the protein level of transforming growth factor-β1 (TGF-β1), p-Smad2, p-Smad3, p-JNK, p-ERK and p-P38 in a time-dependent fashion, indicating that both TGF-β1/Smad2/Smad3 and mitogen-activated protein kinase (MAPK) signaling cascades (a non-Smad pathway) may play essential roles in NiCl₂-dependent EMT as well as cell migration of human lung cancer cells. Furthermore, exogenous NaHS alleviates the NiCl₂-induced EMT and the migration ability of A549 cells only by regulating TGF-β1/Smad2/Smad3, rather than the MAPK, signaling pathway. These results indicate that the exogenous administration of NaHS might be a potential therapeutic strategy against nickel-induced lung cancer progression.

已知镍化合物是常见的环境和职业致癌物，它们也促进肺癌细胞的迁移。但是，分子机理尚待阐明。硫化氢（H ₂ S）与癌症的生物学过程有关。然而，H ₂ S对镍对促进肺癌细胞迁移能力的确切作用和功能尚不清楚。在这项研究中，我们发现氯化镍（NiCl ₂）处理显着下调了内源性H ₂ S酶胱硫醚β-合酶（CBS），胱硫醚γ-裂合酶（CSE）和3-巯基丙酮酸硫转移酶（3- MST）。NiCl ₂之间的相关性诱导上皮-间质转化（EMT）和肺癌A549细胞的迁移能力。外源H ₂ S供体硫化氢钠（NaHS）（100μmol/ L）可以逆转NiCl ₂诱导的EMT以及A549细胞的迁移能力。NiCl ₂处理能够以时间依赖性方式上调转化生长因子-β1（TGF-β1），p-Smad2，p-Smad3，p-JNK，p-ERK和p-P38的蛋白质水平，表明TGF-β1/ Smad2 / Smad3和有丝分裂原激活的蛋白激酶（MAPK）信号级联反应（非Smad途径）都可能在依赖NiCl _2的EMT以及人类肺癌细胞的细胞迁移中发挥重要作用。此外，外源NaHS缓解了NiCl ₂仅通过调节TGF-β1/ Smad2 / Smad3，而不是MAPK信号通路，可以诱导A549细胞的EMT和迁移能力。这些结果表明，外源性给予NaHS可能是针对镍诱导的肺癌进展的潜在治疗策略。