| Background:Prostate cancer is one of the most common malignancies in men,especially in Europe and the United States.The incidence of males is significantly higher than that of Asian men.However,due to the increasing aging of the population and people’s lifestyles being affected by the West,the incidence of prostate cancer in China has been on the rise in recent years.Because the early prostate cancer symptoms are more cryptic and lack specificity,many patients are already in the middle and advanced stages when they found,thus missing the opportunity for surgery.Androgen deprivation therapy(ADT)can be effective in controlling symptoms of androgen-dependent prostate cancer.However,most hormone-sensitive prostate cancers will progress to castration-resistant prostate cancer(CRPC)after two or three years of ADT.Castration-resistant prostate cancer has a short survival time and the patient’s quality of life is also very poor.It is currently the focus and difficulty of clinical treatment.Docetaxel is currently the first-line treatment for CRPC in clinical practice,but because it has some adverse reactions,some patients are difficult to tolerate,or due to drug resistance and other reasons,leading to failure of chemotherapy,so looking for effective joint Medication program is very necessary.Objective:To investigate the synergistic inhibitory effect of Platycodin and Docetaxel on human prostate cancer cell line PC3 and to further explore its molecular mechanism.Methods:MTT assay was used to analyze cell viability of PD and DTX alone or in combination on PC3 cells,and the combination index(CI)were calculated.DAPI staining technique was used to determine whether PD,DTX,and combination therapy could induce apoptosis in PC3 cells.The dual staining of Annexin V and PI was used to detect the apoptosis of PC3 by PD,DTX and combination therapy through flow cytometry.The expression of cleaved PARP,p-mTOR(ser2448),p-EGFR(tyr1068)were detected by western blot to explore the mechanism of PD and DTX in PC3 synergy.The effects of PD and DTX on autophagy of PC3 were determined by the expression levels of Agt5,Beclinl and LC3-Ⅰ/Ⅱ proteinsResults:PD can significantly enhance the sensitivity of PC3 cells to DTX.In the combined effect of 20 μM PD and 20 nM DTX,the growth inhibitory effect of PC3 is the most significant.After the combination of the two drugs,the expression of PARP decreased and the expression of Cleaved PARP increased.Flow cytometry experiments showed that combined use of PD and DTX could increase apoptosis.In terms of mechanism,the synergy of PD and DTX can enhance PD-induced autophagy,but the molecular mechanism of how autophagy shifts to apoptosis remains unclear.Conclusion:The combined use of PD and DTX can inhibit the proliferation of PC3 cells and induce apoptosis,and the combined use of them has a synergistic effect.This study can provide a new pharmacological reference for the treatment of invasive prostate cancer. |
