MGDG extracted from spinach enhances the cytotoxicity of radiation in pancreatic cancer cells.
MGDG extracted from spinach enhances the cytotoxicity of radiation in pancreatic cancer cells.
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DOI：
10.1186/s13014-016-0729-0
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发表时间：
2016-11-22
期刊：
影响因子：
--
通讯作者：
Sasaki R
中科院分区：
文献类型：
--
作者：
Akasaka H;Mizushina Y;Yoshida K;Ejima Y;Mukumoto N;Wang T;Inubushi S;Nakayama M;Wakahara Y;Sasaki R
在我们以前的研究中，从菠菜中纯化的单半乳糖二酰甘油（MGDG）被发现对人类癌细胞系具有细胞毒性作用。本研究进一步评估了MGDG是否可以在体外和体内增强辐射对人胰腺癌细胞的细胞毒性作用。从菠菜干中提取了菠菜糖甘油脂，包括MGDG。采用MTT法检测MGDG对人胰腺癌细胞株MIAPaCa-2、AsPC-1、BxPC-3和PANC-1的细胞毒作用。采用殖民地形成和凋亡实验、western blotting、γ-H2 AX灶染色和彗星实验分析MGDG单独或联合照射对MIAPaCa-2细胞的影响。在小鼠异种移植肿瘤模型中评估对肿瘤生长的抑制作用。MGDG显示出剂量和时间依赖性细胞毒性，72 h时PANC-1、BxPC-3、MIAPaCa-2和AsPC-1细胞的半数最大抑制浓度（IC 50）分别为25.6 ± 2.5、26.9 ± 1.3、18.5 ± 1.7和22.7 ± 1.9 μM。殖民地集落形成实验显示，与单纯放疗相比，MGDG联合放疗组MIAPaCa-2、BxPC-3和AsPC-1细胞集落数明显减少（P < 0.05）。MGDG和辐射的组合诱导MIAPaCa-2细胞中较高比例的凋亡;这种效应与细胞色素c的线粒体释放增加以及裂解的聚（ADP-核糖）聚合酶和半胱天冬酶-3的激活相关。检测到DNA损伤，并且与单独的任一种相比，在接受组合处理的细胞中DNA修复机制更频繁地受损。瘤内注射MGDG联合放疗对肿瘤生长的抑制作用明显优于单用MGDG和放疗（P < 0.05）。这是第一个报告表明，MGDG增强辐射的细胞毒性，诱导癌细胞在体外和体内凋亡。我们的研究结果表明，这种治疗组合可以成为治疗胰腺癌的有效策略。
In our previous study, monogalactosyl diacylglycerol (MGDG) purified from spinach was found to have cytotoxic effects in human cancer cell lines. This study further assessed whether MGDG can enhance the cytotoxic effects of radiation in human pancreatic cancer cells in vitro and in vivo. Glycoglycerolipids from spinach including MGDG were extracted from dried spinach. The cytotoxicity of MGDG were evaluated by the MTT assay using four human pancreatic cancer cell lines (MIAPaCa-2, AsPC-1, BxPC-3 and PANC-1) and normal human dermal fibroblasts (NHDFs). The effects of radiation and MGDG alone or in combination in MIAPaCa-2 cells was analyzed with the colony forming and apoptosis assays, western blotting and cell cycle and DNA damage analyses (γ-H2AX foci staining and comet assay). The inhibitory effects on tumor growth were assessed in a mouse xenograft tumor model. MGDG showed dose- and time-dependent cytotoxicity, with half-maximal inhibitory concentrations (IC50) in PANC-1, BxPC-3, MIAPaCa-2 and AsPC-1 cells at 72 h of 25.6 ± 2.5, 26.9 ± 1.3, 18.5 ± 1.7, and 22.7 ± 1.9 μM, respectively. The colony forming assay revealed fewer MIAPaCa-2, BxPC-3 and AsPC-1 cell colonies upon treatment with both MGDG and radiation as compared to irradiation alone (P < 0.05). The combination of MGDG and radiation induced a higher proportion of apoptosis in MIAPaCa-2 cells; this effect was associated with increased mitochondrial release of cytochrome c and activation of cleaved poly (ADP-ribose) polymerase and caspase-3. DNA damage was detected and DNA repair mechanisms were more frequently impaired in cells receiving the combination treatment as compared to either one alone. Tumor growth was inhibited to a greater degree in mice treated by intratumoral injection of MGDG combined with irradiation as compared to either one alone (P < 0.05). This is the first report demonstrating that MGDG enhances the cytotoxicity of radiation to induce apoptosis of cancer cells in vitro and in vivo. Our findings indicate that this therapeutic combination can be an effective strategy for the treatment of pancreatic cancer.
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影响因子：
5.6
作者：
Kuriyama, I;Musumi, K;Mizushina, Y
通讯作者：
Mizushina, Y
影响因子：
5.2
作者：
Mukubou, Hideyo;Tsujimura, Toshiaki;Ku, Yonson
通讯作者：
Ku, Yonson
DOI：
10.1016/j.ijrobp.2003.11.004
发表时间：
2004-03-15
影响因子：
7
作者：
Koong, AC;Le, QT;Bastidas, JA
通讯作者：
Bastidas, JA
过氧化钛纳米粒子通过体外和体内活性氧生成增强 X 射线照射对胰腺癌模型的细胞毒性作用
DOI：
10.1186/s13014-016-0666-y
发表时间：
2016-07-07
期刊：
Radiation oncology (London, England)
影响因子：
--
作者：
Nakayama M;Sasaki R;Ogino C;Tanaka T;Morita K;Umetsu M;Ohara S;Tan Z;Nishimura Y;Akasaka H;Sato K;Numako C;Takami S;Kondo A
通讯作者：
Kondo A
影响因子：
1.9
作者：
Maeda, Naoki;Kokai, Yasuo;Mizushina, Yoshiyuki
通讯作者：
Mizushina, Yoshiyuki