硫化氢与结直肠癌相关性及其抗肿瘤药物研发的进展

Research progress of the association of hydrogen sulfide with colorectal cancer and its associated anti-tumor drugs

作为最近得到确认的第三个气体信号分子，硫化氢在内环境内具有广泛的生理和病理作用。然而，关于硫化氢在肿瘤、尤其是结直肠癌发生发展中的作用的研究一直存在看似相互矛盾的结果。本文试从硫化氢在低浓度与高浓度作用区间对结直肠癌发生发展的不同作用以及基于硫化氢的抗肿瘤新药研发两个方面，对目前关于硫化氢与结直肠癌的相关研究进展进行综述。目前的研究已经明确了硫化氢在低浓度范围内促进结直肠癌进展以及在高浓度区间抑制肿瘤进展的双相作用模型。针对这种作用特点．硫化氢释放剂、硫化氢合成酶抑制剂以及硫化氢释放基团与NSAID类药物的嵌合体作为抗癌的新型药物得到了广泛研究。综合目前的研究来看，以氨基氧乙酸为代表的硫化氢合成酶抑制剂因其较小的副作用以及较低的作用浓度．相较于其他两类更为有可能发展为新型药物，基于硫化氢与结直肠癌相关性的进一步研究，将为深入揭示结直肠癌的发生机制以及抗肿瘤新药的研发带来新的思路．从而产生巨大的潜在临床价值。

As the third confirmed gaseous transmitters, hydrogen sulfide was found to play a vital role in the eternal milieu both physiologically and pathologically. What＇s intriguing is that, there exists a debate about the role of hydrogen sulfide in the pathogenesis of cancer, especially eolorectal cancer. In this manuscript, progress of the effect of low and high dose hydrogen sulfide on the tumorigenesis of colorectal cancer and research on the antitumor new drugs stemmed from the function of hydrogen sulfide is summarized. Recently, the ＂bell-shape＂ model of the action of hydrogen sulfide illustrated that hydrogen sulfide was able to promote the progression of tumor in low dose and inhibit the progression of tumor in high dose. Based on these results, both hydrogen sulfide synthesis inhibitors and hydrogen sulfide donors （chimeras with NSAIDs） have been widely studied as potential anti-tumor novel drugs. According to the actual results of present studies, hydrogen sulfide synthesis inhibitors featured by aminooxyacetic acid （AOA） is more promising as a novel kind of drug. The future research based on the relationship between hydrogen sulfide and rectal cancer may bring insights into the development of novel anti-tumor drugs, thus producing tremendous potential clinical value.