A role of JAK/STAT pathway on angiogenesis in prostate cell line

Prostate cancer constitutes the first most common type of cancer among men with genitourinary cancers and angiogenesis plays a role in disease progression. Angiogenesis is a complex multistage process regulated by a number of signal transduction pathways. STAT3 is a critical multifunctional mediator and induces expression of genes that regulate some angiogenic factors such as, VEGF, MCL1 and MMPs.In the present research, it is aimed at analysis in prostate cell line, the expression levels of VEGFA, VEGFC, VEGFR2, MMP2 and antiapoptotic factor, the MCL1, which the activated factors through JAK/STAT3 pathway and effects of these genes on inactivation in the development, metastasis and angiogenesis of prostate cancer.In our study, we explored on the LNCaP human prostate cancer cell line, the cytotoxic and apoptotic effects of AG490, S3I-201 and TRAIL on morphological, DNA, RNA (mRNA) and protein levels and for various doses and incubation timeThis is the first study showing that JAK/STAT3 pathway of inhibition, activates the caspase 3 cascade and stimulates apoptosis of the LNCAP cells. It further shows that use of JAK2 inhibitor AG490 or STAT3 inhibitor S3I-201 and TRAİL combination not increase this effect. In conclusion, our study draws attention to the possible clinical effectiveness of use of AG490 or S3I-201 together with chemotherapeutic agents with high cytotoxicity due to the opportunity to attain suitable apoptotic effect with reduced dose and time in cancer treatment targeting JAK/STAT3 pathway. Also, determination of the exact molecular effects of JAK/STAT3 pathway would allow us to identify new molecular targets for the treatment of the prostate cancer