RESUMEN
The development of cisplatin resistance is a common cause of cancer recurrence in colorectal cancer (CRC). Though many studies have reported the oncogenic function of long non-coding RNA (LncRNA) KCNQ1OT1 in multiple cancers, few studies explored its role in cisplatin resistance of CRC. Curcumin is a natural phenolic compound extracted from turmeric, which can effectively suppress cisplatin resistance in CRC. This study aims to expound the role of KCNQ1OT1 in cisplatin resistance in CRC cells and whether KCNQ1OT1 participates in the reversal effect of curcumin on cisplatin resistance in CRC. The interplay between KCNQ1OT1 and miR-497 was determined using RNA pull-down assay and dual-luciferase reporter gene assay. The combination of B-cell lymphoma 2 (Bcl-2) and miR-497 was confirmed using dual-luciferase reporter gene assay. Compared with CRC cell line HCT8, the cisplatin-resistant CRC cell line HCT8/DDP exhibited a higher expression level of KCNQ1OT1. Functionally, the silence of KCNQ1OT1 suppressed proliferation and boosted apoptosis in HCT8/DDP cells. Subsequently, we found that KCNQ1OT1 could act as a sponge of miR-497 and remove the suppressive effect of miR-497 on Bcl-2 expression. Curcumin treatment restrained proliferation and facilitated apoptosis in HCT8/DDP cells. While KCNQ1OT1 overexpression removed the effect of curcumin on HCT8/DDP cells via miR-497/ Bcl-2 axis. Finally, the in vivo experiments showed that the inhibitory effect of curcumin on the growth of cisplatin-resistant CRC cells was reserved by the ectopic expression of KCNQ1OT1. In conclusion, KCNQ1OT1 aggravated cisplatin resistance in CRC cells via the miR-497/Bcl-2 axis. Administration of curcumin could effectively downregulate KCNQ1OT1 expression, thus reversing cisplatin resistance in CRC cells.
Asunto(s)
Cisplatino/farmacología , Neoplasias Colorrectales/metabolismo , Curcumina/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , ARN Neoplásico/metabolismo , Línea Celular Tumoral , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Resistencia a Antineoplásicos/genética , Humanos , Canales de Potasio con Entrada de Voltaje/genética , Canales de Potasio con Entrada de Voltaje/metabolismo , ARN Neoplásico/genéticaRESUMEN
Chemotherapeutic resistance is the main reason of the failure in clinical treatment of gastric cancer. Berberine (BER) is the active compound of traditional Chinese medicine Huang Lian. The aim of this present study is to evaluate the effect of BER on cisplatin resistance in gastric cancer cells and to investigate its possible mechanism. Gastric cancer cell lines SGC-7901 and BGC-823 and their respective cisplatin-resistant variants SGC-7901/DDP and BGC-823/DDP were used in this study. We found that BER treatment significantly reversed cisplatin sensitivity and induced caspase-dependent apoptosis in SGC-7901/DDP and BGC-823/DDP cells; BER treatment induced miR-203 expression, and overexpression of miR-203 mimicked the cisplatin-sensitizing effect of BER. Importantly, we showed that miR-203 was able to target the 3'UTR of Bcl-w. Therefore, we conclude that BER treatment reduces cisplatin resistance of gastric cancer cells by modulating the miR-203/Bcl-w apoptotic axis. BER may be a novel agent to enhance chemotherapeutic responses in cisplatin-resistant gastric cancer patients.
Asunto(s)
Proteínas Reguladoras de la Apoptosis/biosíntesis , Berberina/administración & dosificación , Cisplatino/administración & dosificación , MicroARNs/biosíntesis , Neoplasias Gástricas/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , MicroARNs/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologíaRESUMEN
Background. Functional dyspepsia (FD) is a functional upper gastrointestinal disorder with significant morbidity and medical costs. Previous studies investigated the association of G-protein ß3 (GNB3) genetic polymorphisms with FD but with inconsistent results. Therefore, we performed a meta-analysis to derive a precise estimation of the relationship between GNB3 polymorphisms and FD. Methods. We searched different databases including PubMed, EMBASE, CNKI, and the Ovid Library to gather eligible studies on GNB3 polymorphisms and FD. The association was assessed by the odds ratio (OR) with 95% confidence intervals (CI). Results. We identified 12 studies with 1109 cases and 2853 controls for the analysis. We found no associations of GNB3 C825T polymorphism with FD in the overall population (T versus C, OR = 1.06, 95% CI: 0.96-1.18, P = 0.26; TT versus CC + CT, OR = 1.16, 95% CI: 0.97-1.39, P = 0.11; TT + CT versus CC, OR = 1.01, 95% CI: 0.77-1.31, P = 0.96; TT versus CC, OR = 1.15, 95% CI: 0.93-1.44, P = 0.20). Subgroup analyses by genotyping method indicated that the magnitude of association was strengthened for additive model (OR = 1.15, 95% CI: 1.07-2.24, P = 0.02). Sensitivity analysis did not reveal significant associations under all models. Conclusions. This meta-analysis demonstrates that GNB3 C825T polymorphism may not be a risk factor for FD.
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Pitavastatin classically functions as a blood cholesterol-lowering drug. Previously, it was discovered with antiglioma stem cell properties through drug screening. However, whether it can be used for liver cancer cell therapy has never been reported. In this study, the cell viability and colony formation assay were utilized to analyze the cytotoxicity of pitavastatin on liver cancer cells. The cell cycle alteration was checked after pitavastatin treatment. Apoptosis-related protein expression and the effect of caspase inhibitor were also checked. The in vivo inhibitory effect of pitavastatin on the growth of liver tumor was also tested. It was found that pitavastatin inhibited growth and colony formation of liver cancer Huh-7 cells and SMMC7721 cells. It induced arrest of liver cancer cells at the G1 phase. Increased proportion of sub-G1 cells was observed after pitavastatin treatment. Pitavastatin promoted caspase-9 cleavage and caspase-3 cleavage in liver cancer cells. Caspase inhibitor Z-VAD-FMK reversed the cleavage of cytotoxic effect of pitavastatin. Moreover, pitavastatin decreased the tumor growth and improved the survival of tumor-bearing mice. This study suggested the antiliver cancer effect of the old drug pitavastatin. It may be developed as a drug for liver cancer therapy.
RESUMEN
OBJECTIVE: To investigate the efficacy and feasibility of duodenojejunal bypass(DJB)on non-severe obese patients with type 2 diabetes mellitus(T2DM). METHODS: The body mass index (BMI), fasting plasma glucose(FPG), 2h-postprandial plasma glucose(2hPG), fasting insulin(F-ins), fasting c-peptide(F-CP), glycated hemoglobin and hypoglycemic agents dose changes were tested in 7 patients with non-severe obese T2DM undergoing DJB, preoperatively and within 24 weeks after surgery during the follow-up. Data were collected and the clinical outcomes of T2DM were analyzed. RESULTS: In 7 cases of non-obese T2DM who underwent DJB, one patient was weaned off hypoglycemic agents with normal FPG, 2hPG and HbA1c postoperatively. Five required significantly lower dosage. No significant improvement in 1 case. Complete remission rate of hyperglycemia was 1/7, effective rate was 6/7, and effective rate of HbA1c was 5/7. No significant changes in BMI were observed between the preoperative and postoperative phases. CONCLUSION: Plasma glucose level can be markedly reduced by duodenojejunal bypass in non-obese T2DM, independent of weight loss, and the mechanism remains unclear.
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Cirugía Bariátrica/métodos , Diabetes Mellitus Tipo 2/cirugía , Duodeno/cirugía , Yeyuno/cirugía , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Obesidad , Resultado del TratamientoRESUMEN
AIM: To investigate the feasibility and therapeutic effect of laparoscopic surgery for pyogenic liver abscess (PLA) with biliary pathology. METHODS: From January 2004 to October 2010, 31 patients with PLA combined with biliary pathology meeting entry criteria received surgical management in our hospital. Of the 31 patients, 13 underwent laparoscopic surgery (LS group) and 18 underwent open surgery (OS group). Clinical data including operation time, intraoperative blood loss, postoperative complication rate, length of postoperative hospital stay, and abscess recurrence rate were retrospectively analyzed and compared between the two groups. RESULTS: All patients received systemic antibiotic therapy. Four patients underwent ultrasound-guided percutaneous catheter drainage before operation. Postoperative complications occurred in 5 patients (16.1%, 5/31) including 2 in the LS group and 3 in the OS group. One patient had retained calculus in the common bile duct and another had liver abscess recurrence in the OS group. No retained calculus and liver abscess recurrence occurred in the LS group. In the two groups, there was no mortality during the perioperative period. There were no significant differences in operation time, intraoperative blood loss and transfusion, postoperative complication rate and abscess recurrence rate between the two groups. Oral intake was earlier (1.9 ± 0.4 d vs 3.1 ± 0.7 d, P < 0.05) and length of postoperative hospital stay was shorter (11.3 ± 2.9 d vs 14.5 ± 3.7 d, P < 0.05) in the LS group than in the OS group. CONCLUSION: Laparoscopic surgery for simultaneous treatment of PLA and biliary pathology is feasible in selected patients and the therapeutic effect is similar to that of open surgery.