Department of General Surgery, Xi'an Central Hospital affiliated to the Medical College of Xi'an Jiaotong University, Xi'an, Shanxi, 710003, China.
Department of Gynaecology, Northwest Women's and Children's Hospital affiliated to the Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, 710000, China.
Microb Pathog. 2019 Jan;126:74-78. doi: 10.1016/j.micpath.2018.10.021. Epub 2018 Oct 19.
The present study was aimed to investigate and understand the mechanism of inhibitory effect of phenyl benzoxime on proliferation of SNU-306 cells. Proliferation of SNU-306 cells transfected with wild-type p53-induced phosphatase 1 (Wip1)-siRNA or treated with phenyl benzoxime was examined by 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Induction of apoptosis was examined by flow cytometry using annexin V-fluorescein isothiocyanate/propidium iodide staining. In SNU-306 cells Wip1 mRNA and protein expression was found to be significantly (p < 0.05) higher compared to normal cells. However, Wip1-siRNA transfection significantly (p < 0.02) inhibited the expression of Wip1 at 60 nmol/l. The proliferation of SNU-306 cells was inhibited to 3.7% on transfection with Wip1-siRNA. Phenyl benzoxime reduced proliferation to 92.0, 75.0, 49.0, 19.0 and 4.0% at 1, 2, 4, 8 and 10 μM doses, respectively. The expression of Wip1 was significantly (p < 0.01) suppressed in SNU-306 cells on phenyl benzoxime treatment. Phenyl benzoxime induced apoptosis in 74.73% cells at 10 μM doses compared to 1.34% in control. Treatment with phenyl benzoxime markedly increased the expression of Bax, caspase-3 and p53 and decreased Bcl-2 mRNA. Moreover, addition of SB203580 to cultures of SNU-306 cells significantly (p < 0.01) prevented phenyl benzoxime mediated inhibition of cell proliferation. Phenyl benzoxime induces apoptosis and inhibits SNU-306 cell proliferation by silencing Wip1 expression through p38 MAPK signaling pathway activation. Therefore, phenyl benzoxime can act as an important chemotherapeutic agent for breast cancer treatment.
本研究旨在探讨和了解苯并恶嗪抑制 SNU-306 细胞增殖的作用机制。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）试验检测转染野生型 p53 诱导的磷酸酶 1（Wip1）-siRNA 的 SNU-306 细胞或用苯并恶嗪处理后的细胞增殖情况。通过使用 Annexin V-荧光素异硫氰酸酯/碘化丙啶染色的流式细胞术检测细胞凋亡的诱导。结果显示，与正常细胞相比，SNU-306 细胞中的 Wip1 mRNA 和蛋白表达显著升高（p<0.05）。然而，Wip1-siRNA 转染可显著（p<0.02）抑制 60 nmol/L 时的 Wip1 表达。Wip1-siRNA 转染后 SNU-306 细胞的增殖抑制率为 3.7%。苯并恶嗪在 1、2、4、8 和 10 μM 剂量下分别使 SNU-306 细胞的增殖率降低至 92.0%、75.0%、49.0%、19.0%和 4.0%。苯并恶嗪处理可显著（p<0.01）抑制 SNU-306 细胞中 Wip1 的表达。与对照组的 1.34%相比，苯并恶嗪在 10 μM 剂量下诱导 74.73%的细胞凋亡。苯并恶嗪处理可明显增加 Bax、caspase-3 和 p53 的表达，降低 Bcl-2 mRNA 的表达。此外，向 SNU-306 细胞培养物中加入 SB203580 可显著（p<0.01）阻止苯并恶嗪介导的细胞增殖抑制。苯并恶嗪通过激活 p38 MAPK 信号通路抑制 Wip1 的表达诱导细胞凋亡和抑制 SNU-306 细胞增殖。因此，苯并恶嗪可以作为乳腺癌治疗的一种重要化疗药物。
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