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1.
Anticancer Drugs ; 2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31913196

RESUMO

Gastric cancer (GC) is lethal and there is an urgent need for improved understanding of this disease. Recent studies have reported that microRNAs (miRNAs) play increasingly important roles in the regulation of GC. In this study, we explored the target genes and effects of miR-7641 in GC. Our data showed that high miR-7641 expression was associated with low expression of ARID1A in GC tissue. miR-7641 expression promoted GC cell proliferation and colony formation. Luciferase reporter assay results confirmed that ARID1A was a target gene of miR-7641. Furthermore, downregulation of ARID1A expression caused a significant increase in GC cell proliferation. In vivo depletion of miR-7641 reduced tumor volume and weight and increased ARID1A and Ki67 expression as well as a decreased terminal-deoxynucleotidyl transferase-mediated nick end labeling in mouse tumor tissues. Conversely, ARID1A silencing reversed the suppressive effects of miR-7641 inhibitors on GC cells. Overall, these findings indicate that miR-7641 is a promising novel prognostic biomarker of GC and may represent a novel target for clinical management of GC.

2.
PLoS One ; 10(11): e0142080, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26556485

RESUMO

BACKGROUND: Human pepsinogens are considered promising serological biomarkers for the screening of atrophic gastritis (AG) and gastric cancer (GC). However, there has been controversy in the literature with respect to the validity of serum pepsinogen (SPG) for the detection of GC and AG. Consequently, we conducted a systematic review and meta-analysis to assess the diagnostic accuracy of SPG in GC and AG detection. METHODS: We searched PubMed, Embase, and the Chinese National Knowledge Infrastructure (CNKI) for correlative original studies published up to September 30, 2014. The summary sensitivity, specificity, positive diagnostic likelihood ratio (DLR+), negative diagnostic likelihood ratio (DLR-), area under the summary receiver operating characteristic curve (AUC) and diagnostic odds ratio (DOR) were used to evaluate SPG in GC and AG screening based on bivariate random effects models. The inter-study heterogeneity was evaluated by the I2 statistics and publication bias was assessed using Begg and Mazumdar's test. Meta-regression and subgroup analyses were performed to explore study heterogeneity. RESULTS: In total, 31 studies involving 1,520 GC patients and 2,265 AG patients were included in the meta-analysis. The summary sensitivity, specificity, DLR+, DLR-, AUC and DOR for GC screening using SPG were 0.69 (95% CI: 0.60-0.76), 0.73 (95% CI: 0.62-0.82), 2.57 (95% CI: 1.82-3.62), and 0.43 (95% CI: 0.34-0.54), 0.76 (95% CI: 0.72-0.80) and 6.01 (95% CI: 3.69-9.79), respectively. For AG screening, the summary sensitivity, specificity, DLR+, DLR-, AUC and DOR were 0.69 (95% CI: 0.55-0.80), 0.88 (95% CI: 0.77-0.94), 5.80 (95% CI: 3.06-10.99), and 0.35 (95% CI: 0.24-0.51), 0.85 (95% CI: 0.82-0.88) and 16.50 (95% CI: 8.18-33.28), respectively. In subgroup analysis, the use of combination of concentration of PGI and the ratio of PGI:PGII as measurement of SPG for GC screening yielded sensitivity of 0.70 (95% CI: 0.66-0.75), specificity of 0.79 (95% CI: 0.79-0.80), DOR of 6.92 (95% CI: 4.36-11.00), and AUC of 0.78 (95% CI: 0.72-0.81), while the use of concentration of PGI yielded sensitivity of 0.55 (95% CI: 0.51-0.60), specificity of 0.79 (95% CI: 0.76-0.82), DOR of 6.88 (95% CI: 2.30-20.60), and AUC of 0.77 (95% CI: 0.73-0.92). For AG screening, the use of ratio of PGI:PGII as measurement of SPG yielded sensitivity of 0.69 (95% CI: 0.52-0.83), specificity of 0.84 (95% CI: 0.68-0.93), DOR of 11.51 (95% CI: 6.14-21.56), and AUC of 0.83 (95% CI: 0.80-0.86), the use of combination of concentration of PGI and the ratio of PGI:PGII yield sensitivity of 0.79 (95% CI: 0.72-0.85), specificity of 0.89 (95% CI: 0.85-0.93), DOR of 24.64 (95% CI: 6.95-87.37), and AUC of 0.87 (95% CI: 0.81-0.92), concurrently, the use of concentration of PGI yield sensitivity of 0.46 (95% CI: 0.38-0.54), specificity of 0.93 (95% CI: 0.91-0.95), DOR of 19.86 (95% CI: 0.86-456.91), and AUC of 0.86 (95% CI: 0.52-1.00). CONCLUSION: SPG has great potential as a noninvasive, population-based screening tool in GC and AG screening. In addition, given the potential publication bias and high heterogeneity of the included studies, further high quality studies are required in the future.


Assuntos
Gastrite Atrófica/diagnóstico , Pepsinogênios/sangue , Neoplasias Gástricas/diagnóstico , Biomarcadores/sangue , Detecção Precoce de Câncer , Gastrite Atrófica/sangue , Humanos , Sensibilidade e Especificidade , Neoplasias Gástricas/sangue
3.
World J Gastroenterol ; 21(31): 9337-47, 2015 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-26309359

RESUMO

AIM: To elucidate the potential biological role of miR-30b in gastric cancer and investigate the underlying molecular mechanisms of miR-30b to inhibit metastasis of gastric cancer cells. METHODS: The expression of miR-30b was detected in gastric cancer cell lines and samples by reverse transcription-polymerase chain reaction. CCK-8 assays were conducted to explore the impact of miR-30b overexpression on the proliferation of gastric cancer cells. Flow cytometry was used to examine the effect of miR-30b on the apoptosis. Transwell test was used for the migration and invasion assays. Luciferase reporter assays and Western blot were employed to validate regulation of putative target of miR-30b. RESULTS: The results showed that miR-30b was downregulated in gastric cancer tissues and cancer cell lines and functioned as a tumor suppressor. Overexpression of miR-30b promoted cell apoptosis, and suppressed proliferation, migration and invasion of the gastric cancer cell lines AGS and MGC803. Bioinformatic analysis identified the 3'-untranslated region of eukaryotic translation initiation factor 5A2 (EIF5A2) as a putative binding site of miR-30b. Luciferase reporter assays and Western blot analysis confirmed the EIF5A2 gene as a target of miR-30b. Moreover, expression levels of the EIF5A2 targets E-cadherin and Vimentin were altered following transfection of miR-30b mimics. CONCLUSION: Our findings describe a link between miR-30b and EIF5A2, which plays an important role in mediating epithelial-mesenchymal transition.


Assuntos
Movimento Celular , MicroRNAs/metabolismo , Fatores de Iniciação de Peptídeos/metabolismo , Proteínas de Ligação a RNA/metabolismo , Neoplasias Gástricas/metabolismo , Regiões 3' não Traduzidas , Antígenos CD , Apoptose , Sítios de Ligação , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Biologia Computacional , Bases de Dados Genéticas , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Genes Reporter , Células HEK293 , Humanos , MicroRNAs/genética , Invasividade Neoplásica , Fatores de Iniciação de Peptídeos/genética , Proteínas de Ligação a RNA/genética , Transdução de Sinais , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Fatores de Tempo , Transfecção , Vimentina/genética , Vimentina/metabolismo
4.
Chin Med Sci J ; 30(2): 84-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26148998

RESUMO

OBJECTIVE: To evaluate the prognostic effects of neoadjuvant chemotherapy (NAC) in patients with local advanced gastric cancer. METHODS: We retrospectively analyzed prognosis in 191 patients with advanced gastric cancer, of whom 71 were treated with NAC and 120 received surgery only between February 2007 and July 2013. Postoperative complication rate was recorded. Survival by clinicopathological features, pathological T and N stages, and histopathological tumor regression was retrospectively compared between the two groups. RESULTS: According to Response Evaluation Criteria in Solid Tumors, none of the 71 patients in the NAC followed by surgery group showed complete response, 36 showed partial response, 25 had stable disease, and 10 had progressive disease. The chemotherapy response rate was 50.7%; the disease control rate was 85.9%. Grade 3/4 adverse events were seen in less than 20% patients, with acceptable toxicities. No difference was found in the overall postoperative complication rates between the two groups (7 versus 22 cases, P=0.18). Median survival time was significantly different, at 54 months in the NAC combined with surgery group and 25 months in the surgery-only group (P=0.025). CONCLUSION: In patients with operable gastric adenocarcinomas, NAC can significantly improve overall survival without increasing surgical complications.


Assuntos
Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia
5.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 36(5): 482-7, 2014 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-25360644

RESUMO

OBJECTIVE: To investigate the effects of eukaryotic translation initiation factor 5A2 (EIF5A2) down-regulation by small interfering RNA (siRNA) on aggressiveness of human gastric cancer cell and its potential mechanisms. METHODS: The expressions of EIF5A2 in human gastric cancer cell lines (MKN28 and HGC27) and immortalized gastric mucosal epithelial cells (GES-1) were measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting. EIF5A2 gene in MKN28 cells was silenced by RNA interference and the inhibitory effect was evaluated by both qRT-PCR and Western blotting. Cell proliferation was assessed by CCK-8 assay. Cell migration and invasion were assessed by Transwell assay. The possible downstream targets of EIF5A2, such as CyclinD1, CyclinD3, matrix metallopeptidase-9 (MMP-9), E-cadherin, vimintin, C-myc, and metastasis-associated protein 1 (MTA1) expression levels, were examined by Western blotting. RESULTS: High expressions of EIF5A2 were found in MKN28 cells and human gastric adenocarcinoma tissues. Both EIF5A2 mRNA and protein expression in MKN28 cells were significantly down-regulated by siRNA#1 and siRNA#2, especially siRNA#1. Knockdown of EIF5A2 caused an apparent suppression of MKN28 cell proliferation (all P<0.01), migration (P<0.001), and invasion (P<0.001). After the knockdown of EIF5A2 in MKN28 cells, E-cadherin levels were upregulated, whereas vimentin, Cyclin D1, Cyclin D3, C-myc and MTA1 levels were downregulated. CONCLUSION: Knockdown of EIF5A2 may inhibit MKN28 cell proliferation by downregulating the CyclinD1 and CyclinD3 and suppressing the cell migration and invasion by inhibiting MTA1, C-myc and epithelial-mesenchymal transition.


Assuntos
Fatores de Iniciação de Peptídeos/genética , RNA Interferente Pequeno/genética , Proteínas de Ligação a RNA/genética , Neoplasias Gástricas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Ciclina D1/metabolismo , Ciclina D3/metabolismo , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Genes myc , Histona Desacetilases/metabolismo , Humanos , Interferência de RNA , Proteínas Repressoras/metabolismo
6.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 36(5): 496-500, 2014 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-25360646

RESUMO

OBJECTIVE: To investigate the effect of n-3 polyunsaturated fatty acids (n-3PUFAs) on gut microbiota and endotoxin levels in portal vein of rats fed with a high-fat diet (HFD). METHODS: Thirty-six male Sprague-Dawley rats were randomly divided into four groups and fed with normal control diet (CD), HFD, CD supplemented with n-3PUFAs, and HFD supplemented with n-3PUFAs, respectively. Fresh fecal samples were collected to analyze the gut microbiota 10 weeks after feeding. DNA was exacted from the fresh fecal samples. Quantitative PCR was used to detect the composition of the gut microbiota. The endotoxin levels were detected through modified azo chromogenic substrate limulus amebocyte lysate assay. RESULTS: The differences in body weight before breeding in each group were not statistically significant among these four groups (P=0.613). The increase in the body weight was significantly larger in the HFD group than in the CD group (P=0.0002), CD+n-3PUFAs group (P=0.0001), and HFD+n-3PUFAs group (P=0.022). There were significantly more firmicutes (P=0.002) and enterobacteriales (P=0.022) and significantly less bacteroidetes (P=0.026) and bifidobactera (P=0.034) in the gut of rats from HFD group than those from the CD group. There were significantly more bacteroidetes in the fecal samples of the rats from the CD+n-3PUFAs group compared to those from the CD group (P=0.043). There were significantly more firmicutes (P=0.044)and enterobacteriales (P=0.012) and less bacteroidetes (P=0.042) in the fecal samples of the rats from HFD group compared to those from the HFD+n-3PUFAs group. The endotoxin in plasma form portal vein of rats in HFD group were significantly higher than in CD group (P=0.007) and HFD+n-3PUFAs group (P=0.042) but showed no significant difference between CD+n-3PUFAs and CD group (P=0.210). CONCLUSIONS: HFD can increase body weight and change gut microbiota. Supplementation of n-3PUFAs can partially counteract such gut dysbiosis, lower endotoxin level in portal vein blood, and improve the body weight.


Assuntos
Endotoxinas/sangue , Ácidos Graxos Ômega-3/farmacologia , Intestinos/microbiologia , Microbiota/efeitos dos fármacos , Animais , Peso Corporal , Dieta Hiperlipídica/efeitos adversos , Masculino , Veia Porta , Ratos , Ratos Sprague-Dawley
7.
Asian Pac J Cancer Prev ; 15(15): 6295-300, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25124614

RESUMO

Our aim was to investigate the value of combined detection of serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, CA 242 and CA 50 in diagnosis and assessment of prognosis in consecutive gastric cancer patients. Clinical data including preoperative serum CEA, CA 19-9, CA 242, and CA 50 values and information on clinical pathological factors were collected and analyzed retrospectively. Univariate and multivariate survival analyses were used to explore the relationship between tumor markers and survival. Positive rates of tumor markers CEA, CA 19-9, CA 242 and CA 50 in the diagnosis of gastric cancer were 17.7, 17.1, 20.4 and 13.8%, respectively, and the positive rate for all four markers combined was 36.6%. Patients with elevated preoperative serum concentrations of CEA, CA 19-9, CA 242 and CA 50, had late clinical tumor stage and significantly poorer overall survival. Five-year survival rates in patients with elevated CEA, CA 19-9, CA 242 and CA 50 were 28.1, 25.8, 27.0 and 24.1%, respectively, compared with 55.0, 55.4, 56.4 and 54.5% in patients with these markers at normal levels (p<0.01). In multivariate Cox proportional hazards analyses, an elevated CA 242 level was determined to be an independent prognostic marker in gastric cancer patients. Combined detection of four tumor markers increased the positive rate for gastric cancer diagnosis. CA 242 showed higher diagnostic value and CA 50 showed lower diagnostic value. In resectable gastric carcinoma, preoperative CA 242 level was associated with disease stage, and was found to be a significant independent prognostic marker in gastric cancer patients.


Assuntos
Antígenos Glicosídicos Associados a Tumores/sangue , Biomarcadores Tumorais/sangue , Antígeno CA-19-9/sangue , Antígeno Carcinoembrionário/sangue , Neoplasias Gástricas/diagnóstico , Idoso , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida
8.
PLoS One ; 9(7): e101728, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25006674

RESUMO

PURPOSE: Observational studies have given inconsistent findings on the relationship between intake of dairy products and gastric cancer. We therefore conducted a systematic review with a meta-analysis of observational studies to summarize available evidence on this point. METHODS: We searched the electronic literature databases of PubMed (Medline), EMBASE and the Chinese Biomedical Literature Database up until August 30, 2013. All studies were limited to the English language. Random-effects models were used to pool study results between dairy products consumption and the risk of gastric cancer. We also performed subgroup, publication bias and sensitivity analysis. RESULTS: Eight prospective studies and 18 case-control studies were included in our analysis, with a total number of 7272 gastric cancer cases and 223,355 controls. Pooled relative risks of all studies showed no significant association between dairy intake and gastric cancer (odds ratio [OR]: 1.09, 95% confidence interval [CI]: 0.96-1.25). When study design was separately analyzed, population-based case-control studies showed a positive association between dairy intake and gastric cancer risk (OR: 1.36; 95% CI: 1.07-1.74), whereas no associations were shown by hospital-based case-control studies (OR: 0.86, 95% CI: 0.72-1.02) or cohort studies (OR = 1.01, 95% CI = 0.91-1.13). CONCLUSIONS: The meta-analysis shows that no clear association apparently exists between consumption of dairy products and gastric cancer risk. Further well-designed cohort and intervention studies should be conducted to verify this lack of association.


Assuntos
Laticínios/efeitos adversos , Neoplasias Gástricas/etiologia , Estudos de Casos e Controles , Dieta , Humanos , Estudos Observacionais como Assunto , Razão de Chances , Estudos Prospectivos , Fatores de Risco
9.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 36(2): 214-7, 2014 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-24791805

RESUMO

Gastric cancer is caused by the interaction of genetic and environmental factors. MicroRNA (miRNA) is involved in many cellular processes including proliferation, differentiation, and apoptosis and plays an important role in pathogenesis of gastric cancer, as demonstrated in many recent studies from perspectives including miRNA profiling, reciprocal modulation between epigenetic and miRNA, and Helicobacter pylori infection. MiRNA is highly stabe in blood, and therefore non-invasive diagnosis of gastric cancer using circulating miRNA may be promising.


Assuntos
MicroRNAs , Neoplasias Gástricas , Helicobacter pylori , Humanos , MicroRNAs/metabolismo , Neoplasias Gástricas/genética
10.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 35(4): 373-7, 2013 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-23987481

RESUMO

The prevalence of thyroid cancer has shown an upward trend in China in recent years. Advances in thyroid ultrasound and fine needle puncture cytology have improved the accuracy of the preoperative diagnosis of thyroid cancer. Also,the application of endoscopy-assisted techniques and intraoperative nerve monitoring technology and the further understanding of thyroid lymph node metastasis have made the thyroid surgeries safer and less invasive. This article summarizes the recent advances in the surgical therapy of thyroid cancer.


Assuntos
Neoplasias da Glândula Tireoide/cirurgia , Carcinoma Papilar/cirurgia , Humanos , Radioisótopos do Iodo/uso terapêutico , Terapia de Alvo Molecular , Terapia Neoadjuvante , Neoplasias da Glândula Tireoide/terapia
11.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 35(4): 382-5, 2013 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-23987483

RESUMO

Thyroid cancer is the one of the most common endocrine tumors. The biological behaviors and prognoses of the thyroid cancer of different histological types remarkably differ. The highly invasive thyroid cancer responds poorly to traditional therapies. Recent research advances in the molecular mechanisms of the pathogenesis of thyroid cancer have revealed the roles of many genetic and epigenetic variations such as gene mutation, abnormal gene amplification, and abnormal gene methylation in the development of thyroid cancer, which provides new insights in the molecular diagnosis, prognosis, and target therapy of the thyroid cancer.


Assuntos
Carcinoma/genética , Mutação , Neoplasias da Glândula Tireoide/genética , Humanos , Transdução de Sinais
12.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 35(3): 332-6, 2013 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-23827074

RESUMO

OBJECTIVE: To study the effect of enteral nutrition via jejunostomy catheter on the quality of life in gastric cancer patients who have undergone gastrectomy. METHODS: We retrospectively analyzed clinical data of 104 consecutive patients who had undergone curative resection for gastric cancer in Peking Union Medical College Hospital in 2011.All data were obtained from a prospectively maintained database of gastric cancer.The quality of life was compared between jejunostomy tube group(n=49)and tube-free group(n=55). RESULTS: The two groups were matched in gender,age,tumor size,tumor location,histological type,pTNM stage,type of surgery,body mass index(BMI),quality of life scales,and cycles of postoperative adjuvant chemotherapy(all P>0.05).Also,the global health status(P=0.154),physical function score(P=0.321),role function score(P=0.492),and fatigue symptom score(P=0.845)were not significantly different between these two groups one month after surgery.Three and 6 months after the surgery,patients in the jejunostomy tube group had significantly higher overall health status scores( P<0.001,P=0.038),physical function scores(P=0.004,P=0.005),and role function scores(P=0.002,P=0.038)and significantly lower fatigue symptom scores(P=0.020,P=0.043)when compared to patients from tube-free group. CONCLUSION: Enteral nutrition via jejunostomy catheter can improve the quality of life of gastric cancer patients who have undergone gastrectomy.


Assuntos
Nutrição Enteral , Intubação Gastrointestinal , Qualidade de Vida , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Gastrectomia , Humanos , Jejunostomia , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos
13.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 35(6): 639-44, 2013 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-24382242

RESUMO

OBJECTIVE: To investigate the expression of doublecortin-like kinase 1(DCLK1)in gastric cancer and its prognostic significance. METHODS: The expression of DCLK1 was examined by immunohistochemical staining of paraffin-embedded tumor specimens from 122 patients who underwent curative gastrectomy for gastric cancer at Peking Union Medical College Hospital between July 2002 and December 2006. Survival curves were described by the Kaplan-Meier method and compared by the Log-rank test. Univariate and multivariate analysis was performed with the Cox proportional hazard model. RESULTS: The expression of DCLK1 in tumor cells was significantly upregulated in 51 of 122 patients. High expression of DCLK1 in tumor cells was strongly correlated with pN stage(P=0.029)and lymphovascular invasion(P=0.029). Kaplan-Meier analysis revealed that patients with DCLK1 high expression had a significantly lower 5-year overall survival(OS)rate than that of patients with DCLK1 low expression(39. 0% vs. 65. 8%, P=0.001), as well as a significantly lower 5-year disease-free survival(DFS)rate(37. 0% vs. 64. 5%, P=0.001). Univariate and multivariate analyses showed that DCLK1 expression(both P=0.036)was an independent factor for predicting OS and DFS rate. CONCLUSIONS: High expression of DCLK1 in gastric cancer cells is associated with pN stage and lymphovascular invasion. It may be a predictor for poor survival in patients undergoing surgery for gastric cancer.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Neoplasias Gástricas/metabolismo , Intervalo Livre de Doença , Gastrectomia , Humanos , Estimativa de Kaplan-Meier , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiologia
14.
Zhonghua Wei Chang Wai Ke Za Zhi ; 15(11): 1187-91, 2012 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-23172536

RESUMO

OBJECTIVE: To investigate the effect of the RNAi and the chemotherapy drugs nolatrxed on the expression of thymidylate synthase(TS) and the growth of the colorectal carcinoma LOVO cells. METHODS: The siRNA was constructed targeting the human TS gene, and then transfected into the human colorectal cancer LOVO cells. RT-PCR and Western blot technique were used to observe the TS gene and protein expression levels, and MTT was used to detect cell proliferation after silencing the TS gene. In addition, siRNA and nolatrxed were applied to the LOVO cells to observe the TS protein expression and cell growth. RESULTS: TS siRNA significantly reduced the expression of TS gene and protein in LOVO cells, and inhibited cell growth. The IC50 value of LOVO cells was (1.46±0.25) µmol/L in TS siRNA combined with nolatrexed group, (6.81±0.31) µmol/L in the negative control group, and (6.47±0.43) µmol/L in the single nolatrexed group. After treatment of TS siRNA combined with nolatrexed on LOVO cells for 36 hours, the apoptosis index was higher than that in single TS siRNA and nolatrexed[(62.12±0.89)% vs.(21.56±0.67)% and(40.51±0.83)%, both P<0.05]. CONCLUSION: TS siRNA can partly suppress the expression of TS gene in LOVO cells, inhibit cell proliferation, promote cell apoptosis and enhance cell sensitivity to apoptosis induced by nolatrexd.


Assuntos
Neoplasias Colorretais/patologia , Quinazolinas/farmacologia , Interferência de RNA , Timidilato Sintase/genética , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/enzimologia , Humanos , Timidilato Sintase/metabolismo
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