Reduced succinate dehydrogenase B expression is associated with growth and de-differentiation of colorectal cancer cells

Reduced succinate dehydrogenase B expression is associated with growth and de-differentiation of colorectal cancer cells
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琥珀酸脱氢酶 B 表达减少与结直肠癌细胞的生长和去分化有关

DOI:
10.1007/s13277-013-0781-4
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发表时间:
2013-08-01
期刊:
影响因子:
--
通讯作者:
Shen, Shourong
Shen, Shourong
中科院分区:
其他
文献类型:
--
作者:
Zhang, Decai;Wang, Wei;Shen, Shourong

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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物 II,在细胞生长和体内平衡中发挥重要作用。为了评价SDH在结直肠癌中的表达及功能意义,对4个SDH亚基的表达进行了分析,发现SDHB蛋白在结直肠癌组织中显着降低。对SDHB转染的结直肠癌细胞系SW620进行了体外实验,包括细胞生长测定、集落形成测定、细胞周期分析和裸鼠异种移植。值得注意的是,肿瘤组织中SDHB表达的减少与肿瘤去分化有关,并且SDHB的恢复可以在体外和体内抑制癌细胞的生长。此外,SDHB转染细胞系的cDNA微阵列显示,大多数差异表达基因与细胞周期控制和细胞增殖有关。因此,我们得出结论,人结直肠癌组织中SDHB表达显着降低,结直肠癌中SDHB的重建可能是抑制结直肠癌侵袭性的潜在治疗方法。
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.