Studies On The Mechanism Of Endoplasmic Reticulum-mediated Apoptosis Induced By Dihydroartemisinin In PC-3 Cell Lines Of Prostate Cancer

Objective: To investigate the mechanism of endoplasmic reticulum-mediated apoptosis induced by DHA in PC-3 cell lines of prostate cancer.Methods: PC-3 cells were treated with DHA. The rate of apoptosis and intracellular calcium concentration of PC-3 cell were detected by flow cytomery analysis. Reverse transcription-polymerase chain reation(RT-PCR) was used to measure the expression of mRNA about CHOP,ATF4,ATF6,XBP1,Bcl-2 and Bax. Immunocytochemistry was used to deteched the expression of CHOP protein.Results: The rate of apoptosis increased after DHA treatment in a time and concentration-dependent manne. There was no significant difference in intracellulai calcium concentration of control and solvent group(P>0.05). After 36h treatment of DHA 100μmol·L^-1,the intracellulai calcium concentration increased but no significant defference(P>0.05). I t increased markedly after 48h treatment of DHA(P<0.05). After 8h treatment of DHA 200μmol·L^-1, the intracellulai calcium concentration increased(P>0.05). It increased markedly after 24h and decreased after 36h peak concentration(P<0.05). The expression of CHOP,ATF4,ATF6,XBP1 and Bax mRNA were up-regulated and Bcl-2 mRNA was down-regulated after DHA treatment by RT-PCR analysis. The immunocytochemistry showed up-regulation of protein of CHOP.Conclusion: DHA could activate the three signal passageways of UPR (PERK,IRE1 and ATF6),and induce apoptosis of PC-3 cells. CHOP play an important role in this process. The endoplasmic reticulum stress-mediated apoptotic pathway is involved in this action of DHA. Calcium,Bcl-2 and Bax may be ligaments between ER- and other pathways,but the mechanism is not be confirmed further.