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桑色素通过miR-155/GATA3轴促进前列腺癌细胞对紫杉醇的化学敏感性。

Morin promotes prostate cancer cells chemosensitivity to paclitaxel through miR-155/GATA3 axis.

作者信息

Li Bin, Jin Xunbo, Meng Huilin, Hu Bo, Zhang Tao, Yu Jiang, Chen Shaoan, Guo Xudong, Wang Weiguo, Jiang Wei, Wang Jin

机构信息

Minimally Invasive Urology Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China.

Department of Urology, Jining No.1 People's Hospital, Jining 272011, Shandong, China.

出版信息

Oncotarget. 2017 Jul 18;8(29):47849-47860. doi: 10.18632/oncotarget.18133.

DOI:10.18632/oncotarget.18133
PMID:28599307
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5564610/
Abstract

Paclitaxel is a first-line microtubule-stabilizing drug in treating prostate cancer. However, most patients develop resistance and experience relapse. Morin (3,5,7,20,40-pentahydroxyflavone) is an anti-tumor flavonoid in a numerous types of cancer cells including breast, ovarian and lung cancers. We therefore researched the effects of morin as an adjuvant to paclitaxel in in treating DU145 and PC-3 cells in vitro and DU145 derived prostate cancers in nude mice models. The chemosensitivities of these cells to the treatments of morin and paclitaxel were tested through viability assays utilizing cell counting kit 8 (CCK-8) and apoptosis assays through flow cytometry analyses. MicroRNA (miRNA) microarray was employed to determine the changes in miRNA profile of morin treated DU145 cells. The results from microarrays were further certified by quantitative real-time reverse transcription-PCR (qRT-PCR). The underlying targets of miR-155 were verified using luciferase assays followed by Western blot assays. In the results, morin was capable of repressing the cell viabilities in the paclitaxel-treated cells. MiR-155might be an effective target that can be down-regulated in morin-treated cells. We also discovered that GATA binding protein 3 (GATA3) was directly repressed by miR-155, and the treatment of morin reversed the expression of GATA3. In conclusion, morin might be a potential adjuvant of paclitaxel in treating prostate cancer through regulating miR-155/GATA3 axis.

摘要

紫杉醇是治疗前列腺癌的一线微管稳定药物。然而,大多数患者会产生耐药性并复发。桑色素(3,5,7,20,40 - 五羟基黄酮)是一种在包括乳腺癌、卵巢癌和肺癌在内的多种癌细胞中的抗肿瘤类黄酮。因此,我们研究了桑色素作为紫杉醇辅助药物在体外治疗DU145和PC - 3细胞以及在裸鼠模型中治疗源自DU145的前列腺癌的效果。通过使用细胞计数试剂盒8(CCK - 8)的活力测定和流式细胞术分析的凋亡测定来测试这些细胞对桑色素和紫杉醇治疗的化学敏感性。采用微RNA(miRNA)微阵列来确定经桑色素处理的DU145细胞的miRNA谱变化。微阵列结果通过定量实时逆转录 - PCR(qRT - PCR)进一步验证。使用荧光素酶测定法随后进行蛋白质免疫印迹测定法来验证miR - 155的潜在靶标。结果显示,桑色素能够抑制紫杉醇处理细胞的细胞活力。MiR - 155可能是在经桑色素处理的细胞中可以下调的有效靶标。我们还发现GATA结合蛋白3(GATA3)被miR - 155直接抑制,并且桑色素处理可逆转GATA3的表达。总之,桑色素可能通过调节miR - 155 / GATA3轴成为紫杉醇治疗前列腺癌的潜在辅助药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a27/5564610/cea415accacc/oncotarget-08-47849-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a27/5564610/517631a115ae/oncotarget-08-47849-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a27/5564610/ae3bb8f92cd0/oncotarget-08-47849-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a27/5564610/9aeafb301492/oncotarget-08-47849-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a27/5564610/8838bcba2405/oncotarget-08-47849-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a27/5564610/4bff897df6a1/oncotarget-08-47849-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a27/5564610/cea415accacc/oncotarget-08-47849-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a27/5564610/517631a115ae/oncotarget-08-47849-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a27/5564610/ae3bb8f92cd0/oncotarget-08-47849-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a27/5564610/9aeafb301492/oncotarget-08-47849-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a27/5564610/8838bcba2405/oncotarget-08-47849-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a27/5564610/4bff897df6a1/oncotarget-08-47849-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a27/5564610/cea415accacc/oncotarget-08-47849-g006.jpg

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