Effect Of Triptolide On SENP1 Expression In Prostate Cancer Cells

The worldwide incidence of prostate cancer ranks the second place after lung cancer in male cancers and it tends to gradually increase with age. The mainstay of treatment for advanced prostate cancer (PCa) remains androgen ablation therapy as originally introduced in the early 1940s. Although the vast majority of prostate cancer is hormone-sensitive initially, most patients who are undergoing such therapy can easily transform to hormone-refractory prostate cancer (hormone-refractory prostate cancer (HRPC)) or hormone refractory prostate cancer (androgen-independent prostate cancer, AIPC) over time. Once the cancer progresses to HRPC or AIPC stage, it will spread very quickly thereby hormone therapy no longer curative. From this point on, reliable treatment strategies available are limited.SUMO-specific protease 1 SENP1 is over-expressed in both prostate cancer tissues and cells. Meanwhile, transgenic mice indicate that over-expressed SENP1 leads to development of prostatic intraepithelial neoplasia at an early age. So SENP1 has become a marker of prostate cancer development and potential therapeutic target for prostate cancer. Designing therapeutic agents targeting SENP1 is more effective than androgen ablation therapy in the treatment of advanced PCa, because SENP1 could regulate androgen receptor (AR) activity, which would not lead to the development of androgen-independent cancer. It is important to study relationship between drugs and SENP1 expression in prostate cancer.By using trypan blue staining, MTT staining, and Annexin V-PI double staining, we comprehensively study growth inhibition and apoptosis-inducing effect of triptolide on two human prostate cancer cell lines including androgen-dependent LNCaP cells and androgen-independent PC-3 cells; we detect the change of over-expressed SENP1 mRNA leves in both cells after triptolide treatment utilizing representive real-time quantitative PCR technology. Results show that 0.1μM triptolide has a strong inhibititon effect on prostate cancer cells after exactly the first day of treatment, both two cell lines have stopped growth completely, LNCaP cells are more sensitive to triptolide than PC-3 cells. During apoptosis inspection, after exposure to 0.1μM triptolide for 24h, apoptosis did not occur in PC-3 cells, while exposure to 1μM triptolide, majority of PC-3 cells undergone early apoptosis. In 0.1μM 24h-triptolide-treated LNCaP cells, majority of them were staying in early apoptosis, while exposure to 1μM triptolide for 24h, most of LNCaP cells stepped toward to death. In triptolide-induced apoptosis, LNCaP cells response more sensitively than PC-3 cells, this illustrates that apoptosis induction of triptolide is relavant to its effect on growth inhibition of prostate cancer cells. when considering effect of triptolide on down-regulating SENP1 mRNA levels, we found, exposure to 0.1μM or 1μM triptolide for 24h, SENP1 mRNA levels in LNCaP cells were decreased by 2 times, while SENP1 mRNA levels in PC-3 cells were decreased by about 6 times. This can be explained by the higher SENP1 mRNA levels in PC-3 cells than in LNCaP cells. Predecessors have been confirmed that SENP1 mRNA expression in LNCaP cells is 2.5 times higher than in normal prostatic epithelial cells RWPE1, so down-regulated SENP1 mRNA levels in LNCaP cells is almost equal to that in normal prostate epithelial cells.In summary, triptolide inhibits growth and induce apoptosis of both androgen-dependent and androgen-independent prostate cancer (PCa) cells. In addition, it reduces SENP1 mRNA levels in LNCaP cels to that in normal cells, suggesting its application value in treatment of hormone-refractory prostate cancer.