MnSOD藉由減少氧化壓力以維持癌幹細胞族群

羅勻瑄

doi:10.6342/NTU.2015.01559

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MnSOD藉由减少氧化压力以维持癌干细胞族群

MnSOD reduces ROS stress to maintain cancer stem cell

罗匀瑄 , 硕士　　导师：陈彦荣　　

英文 DOI： 10.6342/NTU.2015.01559

大肠癌；癌干细胞；活性氧化物；猛型超氧化物歧化酶；休眠状态； colon cancer ； cancer stem cell ； reactive oxygen species ； manganese superoxide dismutase ； quiescence

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摘要 │ 参考文献 (65) │ 国际计量

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Colon cancer incidence has been rising due to changes of diet habits and age composition. Surgery, chemotherapy, irradiation, and target therapy are common strategies to treat patients with different stages of colon cancer. However, tumor regrowth, which is called relapse, reduces patients’ survival rate. It was found that a subpopulation exists in colon cancer which is named colon cancer stem cell and endows stem cell-like properties including, self-renewal and limitless division. Colon cancer stem cells could survive in chemotherapy and radiation therapy and reestablish a tumor, which results in relapse. Therefore, colon cancer stem cell is considered as an efficient target for cancer therapy. Several studies reported that colon cancer stem cell may share characteristics with normal stem cells. Among natures of stem cells, reactive oxygen species (ROS) are known to involve in the regulation of cancer cells and stem cells. MnSOD is a superoxide dismutase which locates exclusively in mitochondrial matrix and is believed to be important for controlling the level of cellular ROS. It was found to be important for the fate of stem cell and cancer cell maintenance. However, the role of MnSOD in cancer stem cells is not clear. Therefore, in this study, I used the colon cancer cell line, DLD-1, under the suspension culture as colon cancer stem cells and detected the level of mitochondrial superoxide. The data showed that level of mitochondrial superoxide is higher in cancer stem cells than that in cancer cell pool. I also found that MnSOD expression level is higher in cancer stem cells. Next, we knockdown MnSOD in DLD-1 cell line and examined the population and expression of genes related to cancer stem cells, including CD24, p21, Bmi1, and ABCG2. The result showed that the amount and gene expression of cancer stem cells reduced in the knockdown cell line. Since MnSOD is known to involve in cell cycle regulation, I assumed that changes in MnSOD may disturb the quiescent cancer stem cells. By analyzing proliferation marker and DNA content, I found that the percentage of quiescent population is lower in knockdown cell line. Furthermore, I also found that knowckdown MnSOD impaired cancer cell to re-enter quiescent state by analyzing quiescent population in cells with different culture time. The results suggested that the regulation of mitochondrial superoxide by MnSOD may help in cancer stem cell pool maintenance and re-entry of quiescence. These finding might provide a novel therapeutic target for cancer treatment.

参考文献 ( 65 ) 〈TOP〉

Abid, M. R., I. G. Schoots, K. C. Spokes, S. Q. Wu, C. Mawhinney and W. C. Aird (2004). "Vascular endothelial growth factor-mediated induction of manganese superoxide dismutase occurs through redox-dependent regulation of forkhead and IkappaB/NF-kappaB." J Biol Chem 279(42): 44030-44038.
连结：
Al-Hajj, M., M. S. Wicha, A. Benito-Hernandez, S. J. Morrison and M. F. Clarke (2003). "Prospective identification of tumorigenic breast cancer cells." Proc Natl Acad Sci U S A 100(7): 3983-3988.
连结：
Asselin-Labat, M. L., K. D. Sutherland, F. Vaillant, D. E. Gyorki, D. Wu, S. Holroyd, K. Breslin, T. Ward, W. Shi, M. L. Bath, S. Deb, S. B. Fox, G. K. Smyth, G. J. Lindeman and J. E. Visvader (2011). "Gata-3 negatively regulates the tumor-initiating capacity of mammary luminal progenitor cells and targets the putative tumor suppressor caspase-14." Mol Cell Biol 31(22): 4609-4622.
连结：
Bigarella, C. L., R. Liang and S. Ghaffari (2014). "Stem cells and the impact of ROS signaling." Development 141(22): 4206-4218.
连结：
Borgstahl, G. E., H. E. Parge, M. J. Hickey, W. F. Beyer, Jr., R. A. Hallewell and J. A. Tainer (1992). "The structure of human mitochondrial manganese superoxide dismutase reveals a novel tetrameric interface of two 4-helix bundles." Cell 71(1): 107-118.
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DOI可强化引用精确性、增强学术圈连结，并给予使用者跨平台的良好使用经验，目前在全世界已有超过五千万个对象申请DOI。 如想对DOI的使用与概念有进一步了解，请参考 （ ） 。

DOI可强化引用精确性、增强学术圈连结，并给予使用者跨平台的良好使用经验，目前在全世界已有超过五千万个对象申请DOI。如想对DOI的使用与概念有进一步了解，请参考（）。