Hypochlorite-induced oxidative stress elevates the capability of HDL in promoting breast cancer metastasis.
Hypochlorite-induced oxidative stress elevates the capability of HDL in promoting breast cancer metastasis.
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次氯酸盐诱导的氧化应激提高HDL促进乳腺癌转移的能力
DOI：
10.1186/1479-5876-10-65
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发表时间：
2012-03-30
影响因子：
7.4
通讯作者：
Zheng L
中科院分区：
文献类型：
--
作者：
Pan B;Ren H;Lv X;Zhao Y;Yu B;He Y;Ma Y;Niu C;Kong J;Yu F;Sun WB;Zhang Y;Willard B;Zheng L
背景既往研究表明氧化应激在乳腺癌的发生发展中起着重要作用。 HDL 与乳腺癌的风险和死亡率之间存在显着的负相关关系。然而，众所周知，在氧化应激条件下，例如乳腺癌，HDL可以被氧化修饰，这些修饰可能对HDL的功能产生影响。本研究的目的是确定正常和氧化（由次氯酸盐诱导的氧化应激引起）HDL对乳腺癌细胞转移的不同影响。方法用正常和次氯酸盐氧化HDL处理人乳腺癌细胞系，然后检测细胞体内转移效力以及体外迁移、侵袭、对HUVEC和ECMin的粘附能力。评估整合素表达和 PKC 活性，并应用 PKC 抑制剂和 PKC siRNA。 结果我们发现次氯酸氧化 HDL 显着促进乳腺癌细胞肺转移（乳腺脂肪垫注射 MDA-MB-231 在 P< 0.0 l 时增加 133.4%；尾静脉注射 MCF7 在 P< 0.01 时增加 164.3%）和肝转移 裸鼠体内的转移（通过乳腺脂肪垫注射，MDA-MB-231在P < 0.0 l时增加420％；通过尾静脉注射MCF7，在P < 0.001时增加1840％），并刺激更高的细胞侵袭（MDA-MB-231在P < 0.00 l时增加85.1％；对于MDA-MB-231，在P < 0.00 l时增加88.8％） MCF7;), TC-HUVEC 与正常HDL相比，体外粘附力（MDA-MB-231在P < 0.00 l时增加43.4％；对于MCF7在P < 0.00 l时增加35.2％）和TC-ECM附着（MDA-MB-231在P < 0.00 l时增加41.0％；对于MCF7在P < 0.05时增加26.7％）。数据还表明，PKC通路参与了次氯酸盐氧化HDL的异常作用。结论我们的研究表明，次氯酸盐诱导的氧化应激下的HDL刺激乳腺癌细胞迁移、侵袭、粘附于HUVEC和ECM，从而促进乳腺癌的转移。这些结果表明，应考虑基于 HDL 的治疗来治疗乳腺癌患者。
BackgroundPrevious studies suggest that oxidative stress plays an important role in the development of breast cancer. There is a significant inverse relationship between HDL and the risk and mortality of breast cancer. However, it is well known that under conditions of oxidative stress, such as breast cancer, HDL can be oxidatively modifiedand these modifications may have an effect on the functions of HDL. The purpose of this study is to determine the different effects of normal and oxidized (caused by hypochlorite-induced oxidative stress) HDL on breast cancer cell metastasis.MethodsHuman breast cancer cell lines were treated with normal and hypochlorite-oxidized HDL, and then cell metastasis potencyin vivoand the abilities of migration, invasion, adhesion to HUVEC and ECMin vitrowere examined. Integrin expression and PKC activity were evaluated, and PKC inhibitor and PKC siRNA was applied.ResultsWe found hypochlorite-oxidized HDL dramatically promotes breast cancer cell pulmonary metastasis (133.4% increase atP< 0.0 l for MDA-MB-231 by mammary fat pad injection; 164.3% increase atP< 0.01 for MCF7 by tail vein injection) and hepatic metastasis (420% increase atP< 0.0 l for MDA-MB-231 by mammary fat pad injection; 1840% fold increase atP< 0.001 for MCF7 by tail vein injection) in nude mice, and stimulates higher cell invasion (85.1% increase atP< 0.00 l for MDA-MB-231; 88.8% increase atP< 0.00 l for MCF7;), TC-HUVEC adhesion (43.4% increase atP< 0.00 l for MDA-MB-231; 35.2% increase atP< 0.00 l for MCF7), and TC-ECM attachment (41.0% increase atP< 0.00 l for MDA-MB-231; 26.7% increase atP< 0.05 for MCF7)in vitrocompared with normal HDL. The data also shows that the PKC pathway is involved in the abnormal actions of hypochlorite-oxidized HDL.ConclusionsOur study demonstrated that HDL under hypochlorite-induced oxidative stress stimulates breast cancer cell migration, invasion, adhesion to HUVEC and ECM, thereby promoting metastasis of breast cancer. These results suggest that HDL-based treatments should be considered for treatment of breast cancer patients.
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影响因子：
4.8
作者：
Kimura, T;Tomura, H;Okajima, F
通讯作者：
Okajima, F
DOI：
10.1093/jnci/djh216
发表时间：
2004-08-04
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Furberg, AS;Veierod, MB;Thune, I
通讯作者：
Thune, I
影响因子：
24
作者：
Jafri, Haseeb;Alsheikh-Ali, Alawi A.;Karas, Richard H.
通讯作者：
Karas, Richard H.
DOI：
10.1097/med.0b013e32832922fc
发表时间：
2009-04
期刊：
Current opinion in endocrinology, diabetes, and obesity
影响因子：
--
作者：
Feng H;Li XA
通讯作者：
Li XA
影响因子：
9.7
作者：
KOKOGLU, E;KARAARSLAN, I;BALOGLU, H
通讯作者：
BALOGLU, H