RESUMO
EF24, a curcumin analog, exerts a potent antitumor effect on various cancers. However, whether EF24 retards the progression of triple-negative breast cancer (TNBC) remains unclear. In this study, we explored the role of EF24 in TNBC and clarified the underlying mechanism. In a mouse model of TNBC xenograft, EF24 administration reduced the tumor volume, suppressed cell proliferation, promoted cell apoptosis, and downregulated long noncoding RNA human leukocyte antigen complex group 11 (HCG11) expression. In TNBC cell lines, EF24 administration reduced cell viability, suppressed cell invasion, and downregulated HCG11 expression. HCG11 overexpression reenhanced the proliferation and invasion of TNBC cell lines suppressed by EF24. The following mechanism research revealed that HCG11 overexpression elevated Sp1 transcription factor (Sp1) expression by reducing its ubiquitination, thereby enhanced Sp1-mediated cell survival and invasion in the TNBC cell line. Finally, the in vivo study showed that HCG11-overexpressed TNBC xenografts exhibited lower responsiveness in response to EF24 treatment. In conclusion, EF24 treatment reduced HCG11 expression, resulting in the degradation of Sp1 expression, thereby inhibiting the proliferation and invasion of TNBC cells.
Assuntos
Compostos de Benzilideno/farmacologia , Proliferação de Células/efeitos dos fármacos , Piperidonas/farmacologia , RNA Longo não Codificante/genética , Fator de Transcrição Sp1/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/metabolismo , Animais , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , MicroRNAs/genética , RNA Longo não Codificante/efeitos dos fármacos , Fator de Transcrição Sp1/genética , Fator de Transcrição Sp1/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The majority of the tumors arising from the peripheral nerves of the hand are relatively benign. However, a tumor diagnosed as malignant peripheral nerve sheath tumor (MPNST) has destructive consequences. Clinical signs and symptoms are usually caused by direct and indirect effects of the tumor, such as nerve invasion or compression and infiltration of surrounding tissues. Definitive diagnosis is made by tumor biopsy. Complete surgical removal with maximum reservation of residual neurologic function is the most appropriate intervention for most symptomatic benign peripheral nerve tumors (PNTs) of the hand; however, MPNSTs require surgical resection with a sufficiently wide margin or even amputation to improve prognosis. In this article, we review the clinical presentation and radiographic features, summarize the evidence for an accurate diagnosis, and discuss the available treatment options for PNTs of the hand.