RESUMEN
Resistance to chemotherapy is a main obstacle for effective treatment of gastric cancer, the mechanism of which is still poorly understood. Forkhead box M1 (FoxM1) plays an important role in chemo-resistance of various tumors. This study aimed to explore whether FoxM1 mediated resistance of the gastric cancer cell line SGC7901 to the chemotherapy agent cisplatin (DDP). In the study, we detected FoxM1 and Mcl-1 expression via real time-PCR and western blot and demonstrated that FoxM1 is overexpressed in cisplatin-resistance GC cells and Mcl-1 expression is regulated by FoxM1. We examined SGC7901/DDP cell viability by MTT assay, which revealed that suppression of the FoxM1/Mcl-1 pathway impaired cell viability and thus increased sensitivity to cisplatin in gastric cancer cells. Taken together, the study implied that the FoxM1/Mcl-1 pathway may overcome cispaltin resistance of gastric cancer and provide a new therapeutic target for the treatment of gastric cancer.
Asunto(s)
Antineoplásicos/uso terapéutico , Cisplatino/uso terapéutico , Factores de Transcripción Forkhead/genética , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/efectos de los fármacos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Proteína Forkhead Box M1 , Factores de Transcripción Forkhead/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Humanos , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/biosíntesis , ARN Interferente Pequeño/genética , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Drug resistance remains a major unresolved obstacle for gastric cancer (GC) treatment. Recently, increasing studies have showen that microRNAs (miRNAs) are involved in cancer chemotherapeutic resistance and can potentially be applied to reverse drug resistance in cancers. The relationship between miRNA-149 expression and cisplatin (DDP) resistance in GC cells is still unknown. Here, we detected miR-149 expression by using RT-PCR and found that expression of miR-149 was downregulated in SGC7901/DDP cells compared with SGC7901cells, indicating a role of miR-149 in determining cisplatin-resistance of GC cells. Then, SGC7901/DDP cells were tansfected with miR-149 mimics, MTT assay was performed to determine SGC7901/DDP cell viability, and showed that overexpression of miR-149 inhibited the cell viability after cisplatin treatment, suggesting that up-regulation of miR-149 enhanced SGC7901/DDP cell sensitivity to cisplatin. Furthermore, we confirmed that Forkhead box M1 (FoxM1) is a direct target of miR-149 in SGC7901/DDP cells by using luciferase reporter assay. Besides, we also demonstrated that miR-149 enhances SGC7901/DDP cell sensitivity to cisplatin by downregulating FoxM1 expression. In summary, our data provide new insights that miR-149 plays an important role in determining sensitivity of cisplatin-resistant GC cells by targeting FoxM1 and suggest that miR-149 could be a potential target for reversing drug resistance in GC.