Zhang Decai, Wang Wei, Xiang Bo, Li Nan, Huang Shuo, Zhou Weiwei, Sun Yingnan, Wang Xiaoyan, Ma Jian, Li Guiyuan, Li Xiayu, Shen Shourong
Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, China.
Tumour Biol. 2013 Aug;34(4):2337-47. doi: 10.1007/s13277-013-0781-4. Epub 2013 May 5.
Succinate dehydrogenases (SDH), including SDHA, SDHB, SDHC, and SDHD, form the respiratory complex II in the mitochondria and play an important role in cell growth and homeostasis. In order to evaluate the expression and functional significance of SDH in colorectal cancer, the expression of four SDH subunits was analyzed, and SDHB protein was found to be significantly lower in colorectal cancer tissues. In vitro experiments including cell growth assay, colony formation assay, cell cycle analysis, and nude mouse xenograft of SDHB-transfected colorectal cancer cell line SW620 were performed. Notably, reduced SDHB expression in tumor tissues was associated with tumor de-differentiation, and restoration of SDHB could inhibit the growth of cancer cells both in vitro and in vivo. Furthermore, cDNA microarray of SDHB-transfected cell line showed that most of the differentially expressed genes are related to cell cycle control and cell proliferation. Thus, we conclude that SDHB expression is significantly decreased in human colorectal cancer tissues, and reconstitution of SDHB in colorectal cancer may be a potential therapeutic approach to inhibit aggressiveness of colorectal cancer.
琥珀酸脱氢酶(SDH),包括SDHA、SDHB、SDHC和SDHD,在线粒体中形成呼吸复合体II,并在细胞生长和内环境稳定中发挥重要作用。为了评估SDH在结直肠癌中的表达及功能意义,分析了四种SDH亚基的表达,发现结直肠癌组织中SDHB蛋白显著降低。进行了包括细胞生长测定、集落形成测定、细胞周期分析以及对转染SDHB的结直肠癌细胞系SW620进行裸鼠异种移植等体外实验。值得注意的是,肿瘤组织中SDHB表达降低与肿瘤去分化相关,而SDHB的恢复可在体外和体内抑制癌细胞生长。此外,转染SDHB细胞系的cDNA微阵列显示,大多数差异表达基因与细胞周期调控和细胞增殖有关。因此,我们得出结论,人结直肠癌组织中SDHB表达显著降低,在结直肠癌中重建SDHB可能是抑制结直肠癌侵袭性的一种潜在治疗方法。