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

// Bin Li 1 , Xunbo Jin 1 , Huilin Meng 1 , Bo Hu 1 , Tao Zhang 1 , Jiang Yu 1 , Shaoan Chen 1 , Xudong Guo 1 , Weiguo Wang 2 , Wei Jiang 3 and Jin Wang 4, 5 1 Minimally Invasive Urology Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China 2 Department of Urology, Jining No.1 People’s Hospital, Jining 272011, Shandong, China 3 Department of Urology, Dongying People’s Hospital, Dongying 257091, Shandong, China 4 Department of Urology, Shandong Provincial Qianfoshan Hospital Affiliated to Shandong University, Jinan 250014, Shandong, China 5 School of Basic Medical Sciences, Shandong University, Jinan 250012, Shandong, China Correspondence to: Jin Wang, email: wjinsdu@163.com Keywords: prostate cancer, morin, paclitaxel-resistance, microRNA (miR)-155, GATA binding protein 3 (GATA3) Received: February 28, 2017     Accepted: April 21, 2017     Published: May 24, 2017 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.