Resensitization of Akt Induced Docetaxel Resistance in Breast Cancer by 'Iturin A' a Lipopeptide Molecule from Marine Bacteria Bacillus megaterium.
Resensitization of Akt Induced Docetaxel Resistance in Breast Cancer by 'Iturin A' a Lipopeptide Molecule from Marine Bacteria Bacillus megaterium.
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DOI：
10.1038/s41598-017-17652-z
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发表时间：
2017-12-11
影响因子：
4.6
通讯作者：
Mandal M
中科院分区：
文献类型：
--
作者：
Dey G;Bharti R;Das AK;Sen R;Mandal M
耐药性的产生是肿瘤治疗中的主要问题。多西紫杉醇是一种紫杉醇生物碱，经常用于治疗转移性乳腺癌。然而，耐药性往往限制了这种药物在许多乳腺癌患者中的有效性。操纵耐药细胞使其对多西紫杉醇的治疗效果重新敏感是目前克服这一问题的策略。在这里，我们引入了‘伊图灵A’作为一种有效的化疗增敏剂，用于耐多西紫杉醇的乳腺癌细胞。伊图灵A与多西紫杉醇联合应用可显著抑制多西紫杉醇耐药细胞株MDA-MB-231和MDA-MB-468的增殖。细胞周期分析也显示联合治疗中有大量的凋亡细胞群(SubG0/G1)。在双重药物处理组中，许多凋亡和抗凋亡蛋白发生了明显的改变。Caspase3依赖的细胞死亡在双重处理中观察到。分子机制研究表明Akt及其下游信号通路的过度表达与多西紫杉醇耐药有关。伊图林A显著降低耐药细胞Akt信号通路。这种机制作用可能是伊图灵A对多西紫杉醇耐药的乳腺癌细胞产生化疗增敏作用的原因。总之，伊图灵A通过抑制Akt活性使耐药的乳腺癌细胞对多西他赛治疗重新敏感。
Development of the resistance is the major problem in cancer therapy. Docetaxel is a taxol alkaloid that is frequently used in metastatic breast cancer. However, resistance often limits the usefulness of this drug in many breast cancer patients. Manipulation of resistant cells to re-sensitize to the therapeutic effect of docetaxel is current strategy to overcome this problem. Here, we have introduced ‘Iturin A’ as a potent chemosensitizer in docetaxel resistant breast cancer cells. Combination of Iturin A and docetaxel treatment significantly hampered the proliferation of docetaxel resistant MDA-MB-231 and MDA-MB-468 breast cancer cells. Cell cycle analysis also showed massive amount of apoptotic population (Sub G0/G1) in combination therapy. A number of apoptotic and anti-apoptotic proteins were significantly altered in dual drug treated groups. Caspase 3 dependent cell death was observed in dual treatment. Molecular mechanism study showed that over-expression of Akt and its downstream signaling pathway was associated with docetaxel resistance. Iturin A significantly reduced Akt signaling pathway in resistant cells. This mechanistic action might be the reason behind the chemo-sensitization effect of Iturin A in docetaxel resistant breast cancer cells. In conclusion, Iturin A resensitized the resistant breast cancer cells to docetaxel therapy by inhibiting Akt activity.
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影响因子：
3.7
作者：
Barr MP;Gray SG;Hoffmann AC;Hilger RA;Thomale J;O'Flaherty JD;Fennell DA;Richard D;O'Leary JJ;O'Byrne KJ
通讯作者：
O'Byrne KJ
影响因子：
--
作者：
Dey, Kaushik Kumar;Pal, Ipsita;Mandal, Mahitosh
通讯作者：
Mandal, Mahitosh
影响因子：
120.1
作者：
Dobbelstein, Matthias;Moll, Ute
通讯作者：
Moll, Ute
Caspase 3 介导的癌症放射治疗过程中肿瘤细胞增殖的刺激。
影响因子：
82.9
作者：
通讯作者：
--
DOI：
10.1196/annals.1397.012
发表时间：
2007-01-01
期刊：
SIGNAL TRANSDUCTION PATHWAYS, PT C
影响因子：
--
作者：
Kim, Su-Hyeong;Juhnn, Yong-Sung;Song, Yong-Sang
通讯作者：
Song, Yong-Sang