Effects of proton beam irradiation on mitochondrial biogenesis in a human colorectal adenocarcinoma cell line
Effects of proton beam irradiation on mitochondrial biogenesis in a human colorectal adenocarcinoma cell line
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DOI：
10.3892/ijo.2017.4067
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发表时间：
2017-09-01
影响因子：
5.2
通讯作者：
Shon, Yun Hee
中科院分区：
文献类型：
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作者：
Ha, Byung Geun;Jung, Sung Suk;Shon, Yun Hee
质子束疗法最近被用于改善肿瘤生长的局部控制，并通过减少对正常组织的全局剂量来减少副作用。然而，质子束辐射的生理作用的调节机制还不是很清楚，许多关于这些机制的研究仍在进行中。为了确定质子束对线粒体生物发生的影响，我们研究了线粒体DNA(MtDNA)质量；线粒体转录因子、功能调节因子和动态相关调节因子的基因表达；以及参与线粒体生物发生的信号分子的磷酸化。线粒体DNA/核DNA(NDNA)比值和线粒体染色分析均表明，质子射线照射可促进TPA诱导的侵袭性HT-29细胞线粒体的生物合成。同时，质子辐射增加了线粒体转录因子PGC-1α、NRF1、ERRα和mtTFA，动态调节因子Drp1、OPA1、TIMM44和Tom40，以及功能调节因子CytC、ATP5B和CPT1-α的基因表达。此外，质子辐射增加了AMPK的磷酸化，AMPK是参与线粒体生物发生的重要分子，是一个能量传感器，受AMP/ATP比率的调节。基于这些发现，我们认为质子束照射通过增加TPA诱导的侵袭性HT-29细胞线粒体的生物合成和功能来抑制转移潜能。
Proton beam therapy has recently been used to improve local control of tumor growth and reduce side-effects by decreasing the global dose to normal tissue. However, the regulatory mechanisms underlying the physiological role of proton beam radiation are not well understood, and many studies are still being conducted regarding these mechanisms. To determine the effects of proton beams on mitochondrial biogenesis, we investigated: mitochondrial DNA (mtDNA) mass; the gene expression of mitochondrial transcription factors, functional regulators, and dynamic-related regulators; and the phosphorylation of the signaling molecules that participate in mitochondrial biogenesis. Both the mtDNA/nuclear DNA (nDNA) ratio and the mitochondria staining assays showed that proton beam irradiation increases mitochondrial biogenesis in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced aggressive HT-29 cells. Simultaneously, proton beam irradiation increases the gene expression of the mitochondrial transcription factors PGC-1 alpha, NRF1, ERR alpha, and mtTFA, the dynamic regulators DRP1, OPA1, TIMM44, and TOM40, and the functional regulators CytC, ATP5B and CPT1-alpha. Furthermore, proton beam irradiation increases the phosphorylation of AMPK, an important molecule involved in mitochondrial biogenesis that is an energy sensor and is regulated by the AMP/ATP ratio. Based on these findings, we suggest that proton beam irradiation inhibits metastatic potential by increasing mitochondrial biogenesis and function in TPA-induced aggressive HT-29 cells.