RESUMO
BACKGROUND: Docetaxel was used to treat metastatic CRPC patients. However, Doc resistance in prostate cancer (PCa) hinders its clinical application. OBJECTIVE: To understand the underlying mechanisms by which Doc resistance is developed and to find novel therapeutic target to cure Doc resistant PCa has clinical importance. METHODS: We established Doc resistant cell lines and explored the role of Ezh2 in the development of Doc resistance by overexpressing its cDNA or using its inhibitor. RESULTS: We found that Ezh2 was induced in our established Doc resistant (DocR) cells, which was attributable to the silenced expression of miR-101-3p and miR-138-5p. Blockage of Ezh2 activity by either inhibitor or miRNA mimics could overcome Doc resistance by suppressing Doc-induced cancer stem cells populations. Mechanistically, Ezh2 activity was required for the induced expression of Nanog, Sox2 and CD44 upon Doc treatment. CONCLUSIONS: Targeting Ezh2 could overcome Doc resistance.
Assuntos
Proteína Potenciadora do Homólogo 2 de Zeste/genética , MicroRNAs/genética , Neoplasias da Próstata/tratamento farmacológico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Docetaxel/efeitos adversos , Docetaxel/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Próstata/efeitos dos fármacos , Próstata/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologiaRESUMO
PURPOSE: Laser therapy provides an alternative option for treating non-muscle-invasive bladder cancer (NMIBC). However, the clinical evidence for potassium-titanyl-phosphate (KTP) laser en bloc resection is still limited. Here, we investigated the efficacy and safety of the 120-W front-firing KTP laser for the treatment of NMIBC. METHODS: A total of 64 patients with NMIBC treated with either a 120-W front-firing KTP-photoselective vapo-enucleation of the bladder tumor (PVEBT, n=34) or transurethral resection of the bladder tumor (TURBT, n=30) were included. En bloc resection was applied to the patients in PVEBT group. RESULTS: There was no significant difference in rinsing time (P=0.292), indwelling catheter (P=0.080), pathologic type, and T stage (P=0.870) between the two groups. Compared with the TURBT group, patients treated with PVEBT had a shorter hospitalization stay (P=0.044), a shorter operation time (P=0.008), and a lower muscle miss rate (P=0.044). PVEBT is superior to TURBT in terms of the rate of 1-year recurrence (P=0.015) and tumor grade progression rate (P=0.019). CONCLUSION: The 120-W front-firing KTP laser en bloc enucleation technique is a safe and feasible procedure for treating patients with NMIBC. Further external validation in larger cohorts with a long follow-up period is warranted.