RESUMO
Bladder cancer (BC) is a common and malignant tumor of the urinary tract, and its treatment options are limited. Tectoridin (TEC) has antitumor activity against prostate and colon cancer, but its effects on BC are poorly understood. BC cells were treated with increasing concentrations of TEC, and its effects on cell proliferation, migration, invasiveness, and apoptosis were assessed. Xenograft mouse model was used to evaluate the influences of TEC on BC tumor growth. Western blot analysis was conducted to explore the downstream pathways affected by TEC. TEC treatment decreased BC cell viability in a dose-dependent manner (IC50 ≈ 25 µM), and inhibited cell proliferation, migration, and invasiveness while promoting apoptosis. Clinical analysis revealed high expression of RAB27B in BC tumor tissues, particularly in advanced stages, correlating with an unfavorable prognosis. In vitro experiments demonstrated that TEC suppressed the PI3K/MAPK pathway by targeting RAB27B, and overexpression of RAB27B counteracted the antitumor effects of TEC. In xenograft models, TEC administration suppressed tumor growth, reduced tumor volume, inhibited cell proliferation, and suppressed the PI3K/MAPK pathway, highlighting its potential as an inhibitor of tumor growth. TEC suppresses BC tumor growth by targeting RAB27B and inactivating the PI3K/MAPK signaling and may provide a promising therapeutic target for BC treatment.
Assuntos
Proliferação de Células , Isoflavonas , Fosfatidilinositol 3-Quinases , Neoplasias da Bexiga Urinária , Proteínas rab de Ligação ao GTP , Animais , Feminino , Humanos , Camundongos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosfatidilinositol 3-Quinases/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas rab de Ligação ao GTP/efeitos dos fármacos , Proteínas rab de Ligação ao GTP/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Isoflavonas/farmacologiaRESUMO
Ruthenium-oxo species with high coordination numbers have long been proposed as active intermediates in catalytic oxidation chemistry. By employing a tetradentate bipyridine-bipyrazole ligand, we herein reported the synthesis of a seven-coordinate (CN7) ruthenium(IV) oxo complex, [RuIV(tpz)(pic)2(O)]2+ (RuIVO) (tpz = 6,6'-di(1H-pyrazol-1-yl)-2,2'-bipyridine, pic = 4-picoline), which exhibits high activity toward the oxidation of alkylaromatic hydrocarbons. The large kinetic isotope effects (KIE) for the oxidation of DHA/DHA-d4 (KIE = 10.3 ± 0.1) and xanthene/xanthene-d2 (KIE = 17.2 ± 0.1), as well as the linear relationship between log (rate constants) and bond dissociation energies of alkylaromatics, confirmed a mechanism of hydrogen atom abstraction.