| Objective：Prostate cancer is the most common cancer among men,and the second leading cause of male cancer death in the United States andother developed countries and regions.Although the incidence of prostatecancer in China remains low compared with that in the USA and Europeancountries, it has been increasing in recent years, show a rapidly increasedtrend, affecting seriously the quality of life and level of health in Chinesemen. Because prostate cancer is a kind of hormone-dependent tumor, soendocrine therapy is the preferred treatment for prostate cancer in addition togeneral surgery,.But hormonal therapy is only a palliative treatment，almostall patients gradually become refractory to ADT, progressing tocastration-resistant prostate cancer (CRPC)after experience a median periodof18to24months，and at this stage of disease treatment options are verylimited, then chemotherapy become the primary option of treatment, but theresistance of chemotherapy has limited its efficacy. The resistance ofchemotherapy is a complex process, involving different factors， andautophagy is a newly discovered important factor that could cause theresistance of chemotherapy. Autophagy is also known as type IIprogrammed cell death, involves in the regulation of cell growth and the maintenance of intra-cellular environment. Studies have shown thatautophagy is closely related to tumor progression. Docetaxel (DTX)is asemisynthetic toxoid produced from the needles of the Europeanyew tree, of a wide range of anti-tumor activity that can induce growthinhibition, differentiation and apoptosis of tumor cells, and show a goodclinical efficacy in gastric cancer, cervical cancer, nasopharyngeal cancerand other types of solid tumors.DTX has been widely used in clinicalchemotherapy, but whether DTX could induce autophagy of prostate canceror not have little literature. In this study, we investigate if DTX is able toinduce autophagy in prostate cancer PC-3cells and explore its relationshipwith apoptosis，to provide reference and theoretical basis of making a betterapplication for clinical treatment programs and enhancing thechemosensitivity of prostate cancer to chemotherapeutic agents such asdocetaxel,To investigate the autophagy induced by docetaxel in prostatecancer cell line PC-3, and to explore its possible mechanism，to providetheoretical and experimental basis for clinical application.Methods: The PC-3cells cultured in vitro were treated with docetaxel.The proliferation inhibition rate of PC-3cells was assayed by MTT; Theultra-structural cellular changes were observed by transmission electronmicroscope(TEM);The level of P62and LC-3Ⅱ protein were detected byImmunofluorescence and Western blot,qualitatively and quantitatively; Thelevel of mRNA of autophagy gene Beclin-1was detected by RT-PCR. Results: After docetaxel treatment, the proliferation of PC-3cells wasinhibited effectively. The autophagy could be observed in prostate cancerPC-3cells treated with10-6mol/L docetaxel after24h, the TEM examinationrevealed the appearance of autophagosome with double-membrane structure.Immunofluorescence and Western blot showed the expression of LC-3Ⅱwas increased in PC-3cells after treated with docetaxel, and the expressionof P62was decreased. RT-PCR showed the level of mRNA of Beclin-1wasincreased by docetaxel.Conclusion: Docetaxel could inhibit the growth of PC-3cells andinduce the appearance of autophagy in PC-3cells, and the possiblemechanism of autophagy induced by docetaxel was related to the increase ofBeclin-1mRNA. |
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