RESUMO
RCE-4, a steroidal saponin isolated from Reineckia carnea, has been studied previously and has exhibited promising anti-cervical cancer properties by inducing programmed cell death (PCD) of Ca Ski cells. Considering the cancer cells developed various pathways to evade chemotherapy-induced PCD, there is, therefore, an urgent need to further explore the potential mechanisms underlying its actions. The present study focused on targeting the Bcl-2-Beclin 1 complex, which is known as the key regulator of PCD, to deeply elucidate the molecular mechanism of RCE-4 against cervical cancer. The effects of RCE-4 on the Bcl-2-Beclin 1 complex were investigated by using the co-immunoprecipitation assay. In addition, autophagy-related genes (ATG) were also analyzed due to their special roles in PCD. The results demonstrated that RCE-4 inhibited the formation of the Bcl-2-Beclin 1 complex in Ca Ski cells via various pathways, and ATG 4B proteins involved in this process served as a key co-factor. Furthermore, based on the above, the sensitivity of RCE-4 to Ca Ski cells was significantly enhanced by inhibiting the expression of the ATG 4B by applying the ATG 4B siRNA plasmid.
Assuntos
Apoptose/efeitos dos fármacos , Proteínas Relacionadas à Autofagia/metabolismo , Proteína Beclina-1/metabolismo , Complexos Multiproteicos/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Saponinas/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Apoptose/genética , Asparagaceae/química , Autofagia/efeitos dos fármacos , Autofagia/genética , Proteínas Relacionadas à Autofagia/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Feminino , Humanos , Estrutura Molecular , Complexos Multiproteicos/metabolismo , Fitosteróis/química , Ligação Proteica , Interferência de RNA , Saponinas/química , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologiaRESUMO
OBJECTIVE: To investigate clinical characteristics of multiple myelomaï¼MMï¼ patients with two different results of blood separation in vacum blood collection tubes containing separator gels after centrifugation, and evaluate the prognostic value of these two results. METHODS: The clinical data of 168 patients with newly diagnosed MM treated in our hospital from March 2009 to December 2017 were retrospectively analyzed. The blood samples were divided into control groupï¼the order from top to bottom is serum,separator gel and red blood cellï¼ and abnormal groupï¼the order from top to bottom is serum, red blood cell, separator gel and red blood cellï¼ according to the results of blood separation in vacum blood collection tubes containing separator gels after centrifugation. The differences of age, sex, biochemical indexes (total protein, albumin, immunoglobulin, ß2microglobulin, calcium, lactate dehydrogenase, creatinine), blood routine indexes(hemoglobin, Plt), immunophenotyping and clinical staging of patients were compared; and the relationship between the results of blood separation and efficacy was analyzed and the difference of overall survival (OS) time between the two groups was compared. RESULTS: There was significant difference in total protein, albumin, immunoglobulin, ß2 microglobulin, hemoglobin, immunophenotyping, clinical stage between control group and abnormal group (Pï¼0.05). However the differences of sex, age, calcium, lactate dehydrogenase, creatinine, Plt showed no statistically significant (Pï¼0.05). Patients in abnormal group obtained complete remission (CR) or very good partial remission (VGPR) showed normal results in blood separation after treatment. Patients obtained partial remissionï¼PRï¼ showed partly normalized and partly unchanged, while patients obtained less than PR showed unchanged. Patients in control group obtained less than PR partly showed abnormal results in blood separation after treatment; Patients with normal results in blood separation showed long OS time, while patients with abnormal results of blood separation showed obviously short OS time. CONCLUSION: Abnormal separation phenomenon is found after centrifugation in patients with multiple myeloma, which associates with total protein, albumin, immunoglobulin, ß2 microglobulin, hemoglobin, immunophenotyping, clinical staging and prompts more tumor burden. The result of normal blood separation suggests a better prognosis, while the result of abnormal blood separation suggests a poor prognosis.
Assuntos
Mieloma Múltiplo , Humanos , Imunofenotipagem , Prognóstico , Indução de Remissão , Estudos RetrospectivosRESUMO
Dunaliella salina is a unicellular green alga and possesses two types of photolyase: Class II cyclobutane pyrimidine dimers (CPD) photolyase and (6-4) photolyase. The gene of D. salina (6-4) photolyase is the first one found in unicellular organisms. CPD photolyases have been extensively studied but (6-4) photolyases are less understood. Because of the data observed in this study, D. salina (6-4) photolyase is insensitive to high salinity; whether it can tolerate a higher level of salinity than other (6-4) photolyases needs to be studied further. However, evidence is provided that (6-4) photolyases might be highly conserved among different species, not only in the sequence identity but also in the photorepair mechanism.