【Animal Modeling】-Effect of icariin on androgen receptor signaling pathway in orthotopic prostate cancer xenografts in SCID mice

  OBJECTIVE: To observe the effect of icariin on androgen receptor signaling pathway in orthotopic xenografts of prostate cancer in SCID mice.

  METHODS: 64 male SCID mice were randomly divided into model group, experimental group A, B group and C group. The prostate cancer orthotopic transplantation tumor model was established by intraprostatic injection of human LNCaP prostate cancer cell line suspension. The experimental groups A, B and C were given 10 mg/kg, 40 mg/kg and 80 mg/kg of icariin by intragastric administration for 5 weeks respectively after 2 weeks of modeling, and the model group was given normal saline as a control. RT-PCR was used to detect androgen receptor (AR) and tensin homologous chromosome 10 deletion phosphatase gene (phosphatase and tensinhomologdeletedonchromosometen, PTEN) expression, Western blotting was used to detect prostate cancer specific antigen (Prostate specific antigen, PSA) and phosphorylation AR (p-AR), flow cytometry to detect the cycle of LNCaP prostate cancer cells.

  Results: AR, p-AR and AR mRNA were highly expressed in the model group before and after treatment, and PTEN mRNA was low in expression. The tumor inhibition rate in the model group was lower, and there was no significant difference in tumor mass and tumor volume before and after treatment (P>0.05). After treatment, the tumor inhibition rates of experimental groups B and C reached (42.53±5.72)%, (44.81±4.76)%, ARmRNA, p-AR and PSA were low-expressed, PTENmRNA was high-expressed, and the proportion of cells in G0/G1 phase decreased in both groups. The ratio of cells in S phase increased, and tumor cell proliferation was blocked in S phase, and the difference was significant compared with that before treatment and the model group (P<0.05).

  Conclusion: Icariin may inhibit the proliferation of prostate cancer LNCaP cells by inhibiting AR phosphorylation, enhancing PTEN expression and blocking tumor cell proliferation in S phase.