Objective To study the effects on MCF-7 breast cancer cells with combination of tamoxifen（TAM） and antisense oligonucleotide （ASODN） targeting survivin mRNA. Methods MCF-7 breast cancer cells were treated with a 20 mer ASODN targeting survivin mRNA and TAM, which were divided into three groups: TAM group (treated by TAM only), ASODN group (by ASODN only), and TAM+ASODN combined group (by TAM+ASODN combination). The growth inhibition of MCF-7 cells, the changes of cell cycles and apoptotic rate, the positive rate of survivin mRNA expression, and the activity of caspase-3 were tested by MTT, flow cytometry, hybridization in situ, and spectrophotometric method, respectively.Results The rate of growth inhibition of MCF-7 cells in the TAM+ASODN combined group was (62.26±3.92)%, which was significantly higher than that in the TAM group 〔(42.30±6.63)%〕 or ASODN group 〔(54.77±9.99)%〕, Plt;0.05. The apoptotic rate of MCF-7 cells was (28.08±4.32)% in the TAM+ASODN combined group, which was significantly higher than that in the TAM group 〔(18.94±4.01)%〕 or ASODN group 〔(21.12±3.95)%〕, Plt;0.01. The effect of arresting MCF-7 cells in G0/G1 phase in the TAM+ASODN combined group was ber than that in the TAM or ASODN group (Plt;0.05, Plt;0.01). The positive rate of survivin mRNA in the TAM+ASODN combined group was (13.38±3.45)%, which was significantly lower than that in the TAM group 〔(39.67±7.42)%〕 or ASODN group 〔(27.50±5.80)%〕, Plt;0.01. The activity of caspase-3 in the TAM+ASODN combined group （0.93±0.13） was significantly higher than that in the TAM group (0.50±0.09) or ASODN group (0.64±0.08), Plt;0.01. Conclusion The ASODN targeting survivin mRNA can promote the apoptosis of MCF-7 breast cancer cells, and make MCF-7 cells more sensitive to tamoxifen.
ObjectiveTo systematically review the correlation between the expression of survivin and cervical cancer and its clinical pathologic features. MethodsSystematic and comprehensive literature was searched in The Cochrane Library (Issue 1, 2013), PubMed, MEDLINE (Ovid), CNKI, CBM and WanFang Data from inception to May 2013, to retrieve case-control studies published in the foreign and domestic areas on the correlation between the expression of survivin and cervical cancer and its clinical pathologic features. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted the data, and evaluated the quality of the included studies. Then meta-analysis was conducted using RevMan 5.1 software. ResultsA total of 13 studies involving 1 530 women (658 cervical cancer patients, 563 cervical intraepithelial neoplasis (CIN), 658 normal cervical. The results of meta-analysis showed that, a) as for the positive rate of survivin expression, significant differences were found between cervical cancer and CIN (OR=4.63, 95%CI 3.49 to 6.13, P < 0.000 01), cervical cancer and normal cervical tissues (OR=38.23, 95%CI 23.92 to 61.11, P < 0.000 01), and CIN and normal cervical tissues (OR=9.61, 95%CI 6.11 to 15.09, P < 0.000 01). b) Significant differences were found between clinical stages Ⅰ-Ⅱ and clinical stages Ⅲ-Ⅳ (OR=0.17, 95%CI 0.07 to 0.41, P < 0.000 1), cervical cancer with lymph node metastasis and that without lymph node metastasis (OR=3.57, 95%CI 2.20 to 5.78, P < 0.000 01), high and moderate/low differentiated ESCC tissues (OR=0.31, 95%CI 0.13 to 0.76, P=0.01), and shallow and deep muscular infiltration (OR=0.12, 95%CI 0.02 to 0.68, P=0.02). No significant difference was found between cervical cancer with laterouterus or haemal infiltration and that without latero-uterus or haemal infiltration (OR=24.15, 95%CI 0.07 to 8 199.76, P=0.28). ConclusionCurrent foreign and domestic evidence shows that, survivin expression is significantly correlated to cervical cancer and its clinically pathologic features, which may participate in the whole course of carcinogenesis of cervical cancer, but it is not considered to be an absolute factor for estimating the survival rate of patients with cervical cancer. Due to the quality limitation of the included studies, more large scale, well-designed and high quality studies are needed for further verifying the aforementioned conclusion.
To study the effect of the proliferation and apoptosis of Survivin-T34A mutant on breast cancer MCF-7 cell, we adopted the method of cell culture in vitro to observe the proliferation and apoptosis of the cell. In the experiment, MCF-7 cells were randomly divided into three groups and transfected with normal saline, PORF-9-null and Survivin-T34A, respectively. Breast cancer nude mouse models were established to study anti-tumor effect of Survivin-T34A in vivo. The activity of the cells in the Survivin-T34A-transfected group was lower than that in PORF-9-null group. The increase of cell apoptosis was observed under electron microscopy, meanwhile the apoptotic rate was obviously higher than that in PORF-9-null control by flow cytometry. Tumor inhibition effects of the mouse which received the injection of Survivin-T34A intratumoral injection were apparent, and the inhibition ratio was as high as 47.1%. In conclusion, Survivin-T34A mutant has anti-tumor effect through efficiently inhibiting the growth of breast cancer MCF-7 cell and actively promoting apoptosis of cancer cells.
Objective To systematically review the relationship between the expression of Survivin mRNA and ovarian cancer. Methods PubMed, The Cochrane Library (Issue 11, 2016), CBM, CNKI, VIP and WanFang Data databases were searched to identify case-control studies concerning the association between the expression of Survivin mRNA and ovarian cancer up to November 2016. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.2 software. Results A total of 10 studies were included. The positive of Survivin mRNA in ovarian cancer group was significantly higher than that in control group (OR=24.63, 95% CI 13.44 to 45.15,P<0.000 01). The positive of Survivin in low differentiated group was significantly higher than that in high differentiation group (OR=3.69, 95% CI 2.29 to 5.93,P<0.000 01). The positive of Survivin in clinical stage of Ⅲ-Ⅳ was significantly higher than that in clinical stage of Ⅰ-Ⅱ (OR=4.76, 95% CI 2.99 to 7.57,P<0.000 01), respectively. However, the expression of Survivin mRNA was not associated with lymph node metastasis, ascites and histological type. Conclusion The current evidence indicates that the expression of Survivin mRNA is significantly correlated with ovarian cancer and its clinicopathologic features. Due to the limited quantity and quality of includes studies, the above conclusions are needed to be verified by more high quality studies.
ObjectiveTo systematically review the correlation between Survivin expression and prostate cancer, as well as its clinicopathologic features in Chinese population. MethodsSuch databases as PubMed, EMbase, CBM, CNKI, VIP and WanFang Data were electronically searched from inception to November, 2015 to collect case-control studies about the correlation between Survivin expression and prostate cancer, as well as its clinically pathologic characteristics in Chinese population. Two reviewers independently screened literature, extracted data and assessed the methodological quality of included studies. Then, meta-analysis was performed using RevMan 5.3 software. ResultsA total of 32 case-control studies were included, involving 1613 prostate cancer cases, 708 benign prostatic hyperplasia cases, and 93 controls. The results of meta-analysis showed that the prostate cancer group had a higher Survivin expression level when compared with the benign prostatic hyperplasia group (OR=32.95, 95% CI 19.88 to 54.63, P<0.00001) or the control group (OR=75.78, 95% CI 26.97 to 212.98, P<0.00001). Moreover, the expression level of Survivin was higher in the low and medium differentiation group than in the high differentiation group (OR=4.45, 95% CI 3.13 to 6.32, P<0.00001), higher in the stage of C+D than in the stage of A+B (OR 5.42, 95% CI 2.91 to10.10, P<0.00001), and higher in the prostate cancer with lymph node metastasis than in the prostate cancer without lymph node metastasis (OR 4.07, 95% CI 2.91 to 10.10, P<0.00001). ConclusionCurrent evidence indicates that the expression level of Survivin is significantly correlated with prostate cancer and its clinicopathologic features in Chinese population. Due to the limited quantity and quality of included studies, above conclusions need to be verified by conducting more high quality studies.
Objective To evaluate the expression and clinical significance of Survivin in the tissues of laryngeal carcinoma using meta-analysis. Methods The case-control studies published in China about the expression and association of clinical pathogenic features of Survivin in the tissues of laryngeal carcinoma were electronically retrieved in CBM (1994 to October 2012), CNKI (1994 to October 2012), VIP (1989 to October 2012) and WanFang Data (1996 to October 2012). The reviewers independently identified the literature according to inclusion and exclusion criteria, extracted data, and assessed the quality of the included studies. Then, meta-analysis was performed using RevMan 5.1 software. Results A total of 25 studies were included, involving 1 333 cases of laryngeal carcinoma and 528 cases of health laryngeal mucosa or polyp of vocal cord. The results of meta-analysis showed that, significant differences were found in groups of laryngeal carcinoma vs. health control, laryngeal carcinoma with vs. without lymphatic metastasis, clinical stages I-II vs. III-IV, cell differentiation G1 vs. G2-G3, T1 and T2 stages vs. T3 and T4 stages, and glottic carcinoma vs. non-glottic carcinoma (Plt;0.05). No significant difference was found in groups of age more than 60 vs. no less than 60, male vs. female, and smoke vs. non-smoke (Pgt;0.05). Conclusion Current domestic evidence shows that Survivin may be associated with the whole course of occurrence, advance and transfer of laryngeal carcinoma, and positively correlated to degree of tumor malignance, which may indicate poor prognosis.
Objective To investigate the inhibitory effects of RNA interference (RNAi) expression vector on the expression of survivin in pancreatic cancer cell PANC-1. Methods The protein and mRNA expressions of survivin were examined with immunofluorescence and RT-PCR. The survivin gene was cloned into the T-vector and sequenced. The RNAi expression vectors targeting survivin, named si-svv-1 and si-svv-2 respectively according to whether they harbored a mutation or no mutation, were constructed and transfected into PANC-1 cells with liposome. The expression of survivin mRNA was detected with RT-PCR. Apoptosis of PANC-1 cells was analyzed with DNA ladder and FACS. Results There was a high degree expression of survivin in PANC-1 cells. The expression of survivin was not inhibited by RNAi expression vectors si-svv-1, but inhibited about (72.43±8.04)% by si-svv-2 and the apoptosis rate of PANC-1 cells increased to （12.36±1.44）% after 72 h. Conclusion The RNAi expression vector can effectively inhibit the expression of survivin in pancreatic cancer cell PANC-1 cells and induce the apoptosis in PANC-1 cells.
Objective To investigate the effects and underlying mechanisms of human pituitary tumor-transforming gene 1 (hPTTG1) small interfering RNA (siRNA) on apoptosis of ovarian cancer cell line A2780. Methods hPTTG1 siRNA was transfected into A2780 with lipofectamine (the hPTTG1 siRNA group), and the normal group and the negative control group were set up. Detections were conducted 48 hours after transfection: the interfering efficiency of hPTTG1 mRNA was measured by real-time polymerase chain reaction, the expression of survivin gene and survivin protein was examined by semiquantitative reverse transcriptase-polymerase chain reaction and Western blot, cell apoptosis was detected by DNA fragmentation gel electrophoresis and propidium iodide staining kit, and the activity of caspase-3 was assayed by caspases colorimetric assay kit. Results The expression of hPTTG1 mRNA was expressly inhibited after hPTTG1 siRNA transfection. DNA ladder was observed in the hPTTG1 siRNA group. The apoptotic rate of hPTTG1 siRNA transfection in the hPTTG1 siRNA group was (17.53±2.17)%, higher than those in the normal group and the negative control group [(8.97±1.56)% and (9.64±1.31)%, respectively], with statistically significant differences between them (P<0.05). The expression levels of survivin mRNA and survivin protein were down-regulated. The activity of caspase-3 was raised. Conclusions siRNA targeting hPTTG1 could induce apoptosis of A2780 by inhibition of survivin expression and activation of caspase-3. It may be a potential target for gene therapy of ovarian cancer.
Objective To investigate the inhibitory effect of survivin antisense oligonucleotides (ASODN) on proliferation of pancreatic cancer cells PANC-1. Methods The ASODN and sense oligodeoxynucleotides (SODN) were complementary to survivin sequences. FAM-marked ASODN was transfected into PANC-1 cells mediated by positive ion liposome as ASODN group. Blank control group (normal cells), negative control group (normal medium)， and SODN group were established for comparison. The transfection efficiency was detected by flow cytometry (FCM) after transfection; MTT assay was used to detect cytotoxicity; Cell morphological changes were examined by transmission electron microscopy; The cell cycle and apoptotic rate were analyzed by FCM; Immunohistochemical staining techniques were used, and the expressions of survivin were observed under light microscopy, examined and analysed by computer image. Results ①The transfection efficiency was 31.9%, 37.4%, 41.4%, 52.6%, 24.2%, 11.4%, 16.1%, and 15.5% when the transfecting concentration of ASODN was 50, 100, 150, 200, 250, 400, 600, and 800 nmol/L, respectively; The transfection efficiency was 12.0%, 50.8%, and 11.2% when the inoculated cells was 2×104/well, 2×105/well, and 2×106/well, respectively; The transfection efficiency was 58.8%, 34.0%, and 23.6% when 2 μl, 3 μl, and 4 μl liposome was used during transfection, respectively. ②Cell gap was oversize, morphous was round, adherent cells were less after transfection under fluorescence microscope. ③The inhibition rate in the ASODN group was higher than that in each control group (Plt;0.05) on 24, 36, 48 h after treating by survivin ASODN, which increased as time prolonged (Plt;0.05). ④The apoptosis showed a ladder-shaped line in the ASODN group. ⑤Apoptotic morphology was demonstrated in the ASODN group, such as apoptotic cells with nuclear chromatin highly concentrated, crescent nuclear staining aggregated by the side nuclear membrane, nucleolus disappeared by AO and EB stains. ⑥The apoptotic rate 〔（38.1±3.4）%〕 in the ASODN group was higher than that in the SODN group 〔（4.16±1.7）%〕, Plt;0.05. ⑦G2/M cell cycle arrested in the ASODN group. ⑧After transfection, the expression of survivin protein in the ASODN group was significantly lower than that of each control group (Plt;0.05). Conclusions The optimal transfection conditions are as following: the cell count of 2×105/well, concentration of ASODN 200 nmol/L, and cationic liposome oligofectamine 2 μl, respectively. Survivin ASODN can inhibit the proliferation of pancreatic cancer cells and induce their apoptosis.
Objective To investigate the expressions of X-linked inhibitor of apoptosis protein （XIAP） and survivin in primary hepatocellular carcinoma tissues，and to explore the relationship between them. Methods The expressions of XIAP and survivin protein in 38 primary hepatocellular carcinoma tissues and 16 paracancerous tissues were detected by using immunohistochemistry and the expressions were scored. Results The positive expression rate of XIAP and survivin in primary hepatocellular carcinoma tissues was 81.6% （31/38）and 78.9% （30/38），respctively （P＜0.001）， and in paracancerous tissues was 12.5% （2/16）and 6.3% （1/16）， respectively （P＜0.001）. The score of XIAP expression in the well， middle，and low differentiated tissues of primary hepatocellular carcinoma was （2.91±1.31），（9.27±3.25）， and （13.08±2.26） score， respectively （F=118.948，P＜0.001）， and the score of survivin expression was （4.85±1.83）， （11.08±3.72），and （13.38±1.76） score， respectively （F=72.202，P＜0.001）. They both significantly correlated with the histological grade，but not with the size of tumor（P＞0.05）. There was significantly correlation between the expression intensity of XIAP and survivin in primary hepatocellular carcinoma tissues （r=0.764， P＜0.001）. Conclusions The expression intensity of XIAP and survivin in primary hepatocellular carcinoma tissues are both related with the differentiation of primary hepatocellular carcinoma. The expression intensity of XIAP is related with the survivin， and they may play an important role in the tumor progression and chemical resistances.