Objective To review the application advancements of ATP-binding cassette (ABC) transporter in medical research.Methods Relevant literatures about the applications of ABC families in medical research were reviewed. Results ABC families mainly took roles in transporting substances across cell membrane. Some of them were useful for the prediction of drug resistance and the prognosis of malignant tumors. Others were target s for molecular researches. Their expressions or mutations might be related with the occurrence of diseases. Conclusion ABC families are very important in the diagnosis and therapy for diseases. Thus they are very promising tools for future medical research.
ObjectiveTo explore the in vitro anti-tumor effect of clove extracts (CEs) on radioresistant esophageal cancer cell KYSER and its mechanism.MethodsEthanol extracts of clove bud were prepared. Gas chromatography was used to identify the main active components of CEs. In vitro cell culture method was used to observe the effect of CEs at different concentrations on KYSER cell growth. Methyl thiazolyl tetrazolium (MTT) method was used to detect the effect of different concentration CEs on KYSER’s survival and its’ manner. Transmission electron microscope (TEM) was used to observe the changes of KYSER’s organelle microstructure after CEs treated. Transwell chamber method was used to detect the impact of CEs on KYSER’s migration ability. The apoptosis rate and cell cycle distribution of KYSER treated by CEs were quantitatively determined by flow cytometry. Clone formation experiment was used to detect the clone formation ability of KYSER treaded by CEs.ResultsThe main components of CEs were eugenol, eugenol hydrocarbon, and eugenol acetate. In vitro cell culture showed that 0.4% CEs could inhibit KYSER growth. MTT assay showed that the concentration of CEs≥0.5% could inhibit the survival of KYSER in a dose-dependent manner. TEM assay showed that after treated by 0.5% CEs, KYSER’s microvilli became shorter and wider, ribosomes in the cytoplasm decreased, mitochondria atrophied, and a large number of autophagosomes were formed. Transwell migration assay showed that relative migration rates of KYSER after treated by 0.5% CEs and 0.6% CEs were (65±4)% and (41±3)%, respectively. Compared with the control group, the differences were statistically significant (P<0.001). Flow cytometry showed that the apoptosis rates of the control group, the 0.5% CEs treated group, and the 0.6% CEs treated group were (5.63±0.50)%, (11.77±0.42)%, and (19.44±0.19)%, respectively, and the differences between the control group and the two CEs treated groups were statistically significant (P<0.001). Flow cytometry showed that the G1 phase ratios of cells in the control group, the 0.5% CEs treatment group, and the 0.6% CEs treatment group were (61.99±1.20)%, (75.38±1.50)%, and (78.81±1.00)%, respectively, and the differences between the control group and the two CEs treated groups were statistically significant (P<0.001). The clonal formation experiment showed that after 24 h of CEs treatment, the clonal formation rates of the control group, the 0.5% CEs treatment group, and the 0.6% CEs treatment group were (80.5±1.0)%, (18.1±0.8)%, and (5.0±0.5)%, respectively, and the differences between the control group and the two CEs treated groups were statistically significant (P<0.001).ConclusionCEs can exert anti-tumor effect on radioresistant esophageal cancer cells by inducing autophagy and apoptosis, promoting cell cycle arrest, inhibiting cell energy metabolism, and inhibiting migration.
摘要:目的:探讨2型糖尿病合并糖尿病足患者与胰岛素抵抗的关系。方法:205例2型糖尿病患伴糖尿病足患者作为观察组,无足部病变的糖尿病患者作为对照组,观察其体重指数、空腹血糖、胰岛素、血脂等指标,两组间进行比较并相关性分析、多元回归分析。胰岛素抵抗指数(HOMAIR)=FPG×FIns/22.5。结果:糖尿病足患者的HOMAIR显著高于无糖尿病的患者(Plt;0.05)。多元回归分析显示糖尿病病程、LDL及BMI是影响2型糖尿病足患者胰岛素抵抗的主要危险因素。结论:糖尿病足患者存在着更严重的胰岛素抵抗。Abstract: Objective: To discuss the relationship between diabetes and pedopathy of type II diabetes and insulin resistance. Methods:The diabetes type II patients were divided into group A (combined with pedopathy) and group B (without pedopathy). The blood glucose and insulin of empty stomach, BMI,Alc and lipid were detected. The insulin resistance index (HOMAIR) was calculated and compared between two groups. Results:The HOMAIR was higher in group A than that in group B (Plt;0.05).The duration of disease,LDL and BMI was positive related with diabetes pedopathy. Conclusion:The insulin resistance was more worse in pedopathy of Type II diabetes.
Objective To dynamically study the formation of multidrug resistance(MDR) of human hepatocellular carcinoma cell SMMC-7721 induced by Adriamycin (ADM) and the role of multidrug resistance-associated protein(MRP) in its mechanisms.Methods Hepatocellular carcinoma cell SMMC-7721 was cultured in RPMI-1640 medium containing ADM with progressively increased concentration or directly cultured in medium containing different concentrations of ADM. Resistant index of drug-resistant variants of SMMC-7721 cell was determined by drawing cell dosage-reaction curves.Levels of MRP mRNA expression were detected by reverse transcription-polymerase chain reaction(RTPCR). Intracellular rubidomycin(DNR) concentration was examined by flow cytometry(FCM).Results With progressive increasing of ADM concentration in medium resistant index and levels of MRP mRNA expression were correspondingly increased but intracellular DNR concentration was markly reduced. When parental cells were directly cultured in medium containing different concentrations of ADM, the higher the ADM concentration, the higher the level of MRP mRNA expression, but intracellular DNR concentration was kept at the similar high level and most cells died. Conclusion ADM may progressively induce SMMC-7721 cell resistant to multiple chemotherapeutic drugs with reduced intracellular DNR accumulation associated with the overexpression of MRP gene.
Multidrug resistance (MDR) remains the major obstacle to the success of clinical cancer chemotherapy. P-glycoprotein (P-gp), encoded by the MDR1, is an important part with complex mechanisms associated with the MDR. In order to overcome the MDR of tumors, we in the present experimental design incorporated small interfering RNA (siRNA) targeting MDR1 gene and anticancer drug paclitaxel (PTX) into the solid lipid nanoparticles (SLNs) to achieve the combinational therapeutic effects of genetherapy and chemotherapy. In this study, siRNA-PTX-SLNs were successfully prepared. The cytotoxicity of blank SLNs and siRNA-PTX-SLNs in MCF-7 cells and MCF-7/ADR cells were detected by MTT; and the uptake efficiency of PTX in MCF-7/ADR cells were detected via HPLC method; quantitative real-time PCR and flow cytometry were performed to investigate the silencing effect of siRNA-PTX-SLNs on MDR1 gene in MCF-7/ADR cells. The results showed that PTX loaded SLNs could significantly inhibit the growth of tumor cells, and more importantly, the MDR tumor cells treated with siRNA-PTX-SLNs showed the lowest viability. HPLC study showed that SLNs could enhance the cellular uptake for PTX. Meanwhile, siRNA delivered by SLNs significantly decreased the P-gp expression in MDR tumor cells, thus increased the cellular accumulation of rhodamine123 as a P-gp substrate. In conclusion, the MDR1 gene could be silenced by siRNA-PTX-SLNs, which could promote the growth inhibition efficiency of PTX on tumor cells, leading to synergetic effect on MDR tumor therapy.
Objective To investigate the reversal effect of antisense phosphorothioate oligonucleotide （ASOND) on human hepatoma resistant cells. Methods Human hepatoma resistant cells SMMC-7721 was transfected with synthetic antisense phosphorothioate oligonucleotide complementary to the 5′ region flanking the AUG initiation codon mediated by lipofectamine. In vitro drug sensitivity was measured by MTT assay. The expression of P-170 was determined by flow cytometry and mRNA was assessed by RT-PCR. Results ASOND inhibited the expression of mRNA and p-170 in SMMC-7721, enhanced the sensitivity of SMMC-7721 to chemotherapeutic drug. The best inhibitory effect was achived by the dose of 0.5μmol/L. Conclusion ASOND enhanced the sensitivity of SMMC-7721 to chemotherapeutic drug and reversed the multidrug resistance of SMMC-7721 partially.
ObjectiveTo evaluate the relationship between the expression of alpha fetoprotein (AFP) and chemoresistance in hepatocellular carcinoma.MethodsHepatocellular carcinoma was screened from liver tumor tissue samples, which was obtained by puncture before transcatheter arterial chemoembolization (TACE). Immuno-histochemical staining was used to detect the expression of AFP in HCC tissues and the effect of AFP expression in HCC on the effect of chemotherapy was analyzed.ResultsA total of 62 patients met the inclusion criteria, of which 36 were in the chemotherapy resistant group and 26 in the chemotherapy sensitive group. There were 42 patients with positive expression of AFP in tumor tissues (including 29 patients with chemoresistance) and 20 patients with negative expression of AFP in tumor tissues (including 7 patients with chemoresistance). There were no significant difference between the two groups in sex, age, tumor differentiation, Child-Pugh classification of liver function, tumor size, tumor site and hepatitis (P>0.05). In elevated serum AFP level, tumor single, and with portal vein tumor thrombus (PVTT), the proportion of patients in the chemosensitivity group were significantly lower than that in the chemosensitivity group (P<0.05). The results of logistic multivariate regression analysis showed that positive expression of AFP ［OR=0.280, 95%CI (0.092, 0.950), P=0.045］ and PVTT ［OR=0.026, 95%CI (0.004, 0.322), P=0.005］ were independent risk factors for chemotherapeutic resistance in hepatocellular carcinoma.ConclusionAFP positive expression in liver tumor tissues and PVTT are useful indicators of resistance to chemotherapy.
Objective To review the recent studies on the multidrug resistance of breast cancer. Methods The literatures of recent years on the studies of multidrug resistance, multidrug resistance protein and breast cancer resistance protein were reviewed. Results Multidrug resistance resulted from multiple factors. How to identify the sensibility of chemotherapy drugs and select individual therapeutic regime early were important to improve the survival rate and life quality of breast cancer patients. Conclusion These studies on multidrug resistance of breast cancer are helpful to predicting the effect and outcome of chemotherapy and overcoming the barrier of drug resistance.
Objective To observe the effect of resveratrol on multidrug resistance (MDR) in human retinoblastoma cells treated. Methods RB cells in logarithmic growth phase were divided into experimental group and control group. RB cells in experimental group were cultured with different concentrations of resveratrol (6.25, 12.50, 25.00, 50.00, 100.00 mu;mol/L) for 24 and 48 hours. The proliferation (absorbance value) was assayed using methyl thiazolyl tetrazolium (MTT). RB cells were cultured with 50.00 mu;mol/L resveratrol for 48 hours. The expressions of MDR-1, cyclooxygenase-2 (COX-2)、multidrug resistance-associated protein-1 (MRP-1), glutathione-S-transferases-pi; (GST-pi;) were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. The RB cells of the control group were cultured with 0.5% dimethyl sulfoxide. Results Compared with the control group, the absorbance value decreased in experimental groups (6.25, 12.50, 25.00, 50.00 mu;mol/L) in a dose dependent manner (F=4.782，P＜0.05). The difference of absorbance value between 50.00 and 100.00 mu;mol/L experimental groups was not significant (F=6.351,P＞0.05). Compared with the control group, the mRNA (t=9.170, 5.758, 4.152, 4.638) and protein (t=3.848, 5.955, 4.541, 3.514) expression levels of MDR-1, MRP1, COX-2, and GST-pi; decreased in the experimental group (P＜0.05). Conclusion Resveratrol can down-regulate the expression of MDR in RB cells.
ObjectiveTo explore the relationship between mdr1 gene expression of hepatocellular carcinoma (HCC) and pathological characteristics,chemotherapy and prognosis. MethodsThe mdr1 gene expression of HCC in 56 patients with the methods of immunohistochemistry was studied. The results were analysed with the pathological data by statistic methods. ResultsThe positive expression of mdr1 gene in cancer tissues and pericancerous tissues of HCC were 30/56(53.6%) and 19/56 (33.9%) respectively. The difference was statistically significant (χ2=4.39,P＜0.05). The positive expression of mdr1 gene in cancer tissues of untreated patients and in recurrent patients were 22/48(45.8%) and 8/8(100%) respectively.The expression of mdr1 gene was not associated with tumor size, number, tumor thrombus, differentiation, HBsAg and liver cirrhosis. The patients with positive mdr1 expression had a shorter survival time than that of negative ones. But the difference was not statistically significant. Conclusion The positive expression of mdr1 in HCC is 53.6%. It is not associated with tumor size, number, tumor thrombus, tumor differentiation, HBsAg and liver cirrhosis. There are innate multidrug resistance in HCC.