• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제34권1호
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• pp.71-82
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• 2008

Survivin is a member of the inhibitors of apoptosis (IAP) family that have been known to inhibit activated caspases in apoptosis. In contrast to most IAP family members, survivin mRNA is expressed during fetal development, is not found in normal adult tissues and is overexpressed again in the cancer. Though survivin expression has been documented in most human cancers, little is known about its expression in OSCC and its potential value as a predictor of cancer survival. The purpose of this study was to investigate survivin expression in OSCC and to evaluate its value as a prognostic marker. We evaluated survivin expressions in cancer lines and OSCC samples and investigated the relationships between survivin expressions and clini-co-pathological parameters including stage, differentiation, proliferation, lymph node metastasis, blood vessel density, and gelatinolytic activity. With immunohistochemistry, we analyzed survivin expression in 38 OSCCs. Patients' clinico-pathological parameters and their survival rate were analyzed to reveal their correlations with Survivin expressions. We cultured oral cancer cell lines and evaluated the correlation between gelatinolytic activities and survivin expressions of them. Survivin protein was observed both in nuclei and cytoplasm of tumor specimens while little or not observed in normal gingival mucosal tissues. Additionally, survivin expressions were correlated with lymph node metastasis, tumor proliferation and survival rate. Survivin expression was observed in 100% of 38 samples of OSCC and its expression levels are statistically associated with the proliferative activity of the tumors, lymph node metastasis and the survival of the patients. Based on these results, survivin is commonly expressed in OSCC and may thus provide valuable prognostic information related with lymph node metastasis, proliferation and survival rate as well as a potential therapeutic target in OSCC.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6233-6237
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• 2012

Survivin, a new member of the inhibitor of apoptosis protein (IAP) family, both inhibits apoptosis and regulates the cell cycle. It is overexpressed in breast tumor tissues. In this study, we designed two survivin specific DNAzymes (DRz1 and DRz2) targeting survivin mRNA. The results showed that DRz1 could decrease the expression of survivin by nearly 60%. Furthermore, DRz1 significantly inhibited cell proliferation, induced apoptosis and inhibited migration in MCF-7 cells. In addition, down-regulation of survivin expression was associated with increased caspase-3 and -9 activities in MCF-7 cells after 24 h transfection. In our experiments, the efficacy of DRz1 to influence survivin levels and associated effects were better than DRz2. Survivin-DRz1 might have anti-tumorigenic activity and may potentially provide the basis for a novel therapeutic intervention in breast cancer treatment.

• Tuberculosis and Respiratory Diseases
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• 제48권6호
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• pp.909-921
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• 2000

연구배경 : 최근 아포프토시스를 억제하는 단백질들에 대한 관심이 증가하고 있다. 이 중 IAP(inhibitor of apoptosis protein) 가족군의 일원인 survivin은 태아 사기에는 높은 발현율을 보이지만 생후 정상 분화된 조직에서는 거의 발현이 되지 않고 암세포로 변환이 되면 그 발현이 증가하는 것이 보고되고 있다. 대장암 및 위암을 대상으로 한 연구에서 survivin의 발현이 아포프토시스 지수의 감소와 연관이 있으며 대장암에서 survivin의 과발현이 나쁜 예후와 연관성이 있다고 보고한 바 있으나 추후 보완 연구가 필요한 상황이며, 폐암을 대상으로 한 연구결과는 아직 보고되지 않고 있다. 이에 수술적으로 절제된 비소세포폐암 병리조직 29예를 대상으로 survivin에 대한 면역조직화학적 연구를 시행하여 survivin의 종양특이적 발현 및 임상적 의의에 대한 분석을 시행하였다. 방법 : 수술절제된 29예의 비소세포폐암의 포르말린 고정조직을 파라핀 포매한후 $4{\mu}m$ 절편으로 잘라 면역조직화학 염색을 시행하였다. 일차항체로 antisurvivin polyclonal antibody를 이용하였고, 아포프토시스에 중요한 역할을 하는 p53과의 관련성을 분석하기 위하여 anti-p53 monoclonal antibody를 이용한 면역조직화학 염색도 병행 시행하였다. 발현 정도는 양성염색부위의 면적과 염색 강도에 따라 점수화한 뒤 합산한 접수로 판정하였다. 사용된 sntisurvivin antibody의 특이성 및 암특이적 발현을 확인하기 위하여 폐암부위와 주변 정상 폐부위로 분리되어 보존되어 있는 신선동결조직에서 단백질올 추출하여 Western blot을 시행하였다. 각각의 임상적 지표들과 survivin 발현과의 연관성은 chi-square test를 이용하여 비교하였고 Kaplan-Meier 방법으로 생존 곡선을 얻었으며 이 두 군간의 생존함수의 통계적 분석은 generalized Wilcoxon test로 하였다. 결과 : 면역조직화학 염색을 시행한 29예 중 20예(69.0%)에서 암세포 특이적 survivin의 발현이 관찰되었다. 폐암 조직과 정상 폐 조직으로 시행한 Western blot으로 암특이적 survivin의 발현을 확인하였다. 그러나 survivin의 발현 여부에 따른 연령, 조직학적 분류, 병기, 재발율 등과는 유의한 차이가 없었으며 생존 곡선에서도 통계적 유의성은 없었다. p53 발현과 survivin 발현 정도와도 통계적 유의성을 확인할 수 없었다. 결론 : 연역조직화학적 분석과 Western blot을 이용하여 비소세포폐암에서 survivin의 암 특이적 발현을 확인할 수 있었지만 survivin의 발현정도와 조직학적 분류, 병기, 재발율, 생존율 등 임상지표들과는 통계적 유의성올 관찰할 수 없었으며 p53 발현과도 유의한 상관성이 없었다.

• Journal of Korean Neurosurgical Society
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• 제40권1호
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• pp.1-5
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• 2006

Objective : Survivin is an inhibitor of apoptosis protein[IAP], which inhibits apoptosis through a pathway distinct from the Bcl-2 family members. Overexpression of survivin and Bcl-2 have been commonly reported in human neoplasms. The authors investigate whether there is a synergistic effect on the anti-apoptosis rate of primary brain tumors "in situ" based on the co-expression of survivin and Bcl-2. Methods : One hundred and two brain tumor patients who had been resected were included in this study. Survivin tin and Bcl-2 were detected by Western blotting analysis, while apoptosis was examined by DNA fragmentation analysis. An anti-apoptotic rate was assessed in these brain tumor samples based on the expression of survivin and Bcl-2 or co-expression of both. Results : Survivin and Bcl-2 were expressed in 57[55.9%] and 53[52.0%] of 102 brain tumor samples studied respectively, and co-expressed in 31[30.4%]. The percentage of astrocytic and meningeal tumors expressing survivin was significantly correlated with histological grades; however, Bcl-2 was not correlated [p=0.106]. The anti-apoptotic rate in primary brain tumors with survivin, Bcl-2, and both was detected in 49[86.0%] of 57 samples, 42[79.9%] of 53 samples, and 27[87.1%] of 31 samples, respectively. Their difference in the frequency of anti-apoptosis was not significant. Conclusion : Survivin or Bcl-2 is involved in the anti-apoptosis. However, it suggests that co-expression of survivin and Bcl-2, together, have no synergistic effect on the anti-apoptotic properties of the primary brain tumors.

• Journal of Gastric Cancer
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• 제3권1호
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• pp.19-25
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• 2003

Purpose: Dysregulation of apoptosis may attribute to development of cancer by abnormally prolonging cell viability with accumulation of transforming mutations. Survivin and HIAP (Human Inhibitors of Apoptosis)-1 were recently described as apoptosis inhibitors. Their pathogenic roles in gastric cancer are largely unknown. In the present study, we examined the expression of survivin and HIAP-1 in gastric cancer tissues and cell lines in order to elucidate the roles of survivin and HIAP-1 in the process of gastric carcinogenesis. Materials and Methods: Eight gastric cancer cell lines and five gastric cancer tissues were studied. The expression of survivin and HIAP-1 were evaluated by reverse transcription -polymerase chain reaction (RT-PCR), immunohistochemistry, and Western blot. Results: Western blot and RT-PCR analysis revealed survivin and HIAP-1 expression in all gastric cancer cell lines. Increased expression of survivin and HIAP-1 were found in all cases of gastric cancer tissues compared to normal tissues by Western blot analysis. In immunohistochemical analysis tumor cells were stained with anti-survivin and anti-HIAP-1 antibodies. Cell cycle dependence of survivin expression was preserved in gastric cancer cell lines. Conclusion: The results indicate that increased expression of survivin and HIAP-1 genes may play an important role in gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5467-5472
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• 2013

Objective: To construct short hairpin RNA (shRNA) eukaryotic expression vectors targeting Livin and Survivin genes, and to explore the impact of co-transfection of Livin and Survivin shRNA expression vectors on the biological behavior of HepG2 cells. Methods: shRNA eukaryotic expression vectors pSD11-Livin and pSD11-Survivin were designed and constructed then transfected into HepG2 cells separately or in combination. mRNA and protein expression in transfected cells was assessed by quantitative fluorescence PCR and Western blotting, respectively. Cell proliferation was measured by MTT assay and cell apoptosis by TUNEL assay. Results: The Livin and Survivin shRNA eukaryotic expression vectors were successfully constructed and transfected into HepG2 cells. The relative mRNA expression levels of Livin and Survivin in HepG2 cells co-transfected with pSD11-Livin and pSD11-Survivin were $0.12{\pm}0.02$ and $0.33{\pm}0.13$, respectively, which was significantly lower than levels in cells transfected with either pSD11-Livin or pSD11-Survivin (P<0.05). The relative protein expression levels of Livin and Survivin in the co-transfected cells were also significantly decreased compared to single-transfection (P<0.05). The inhibition rate of cell growth in the co-transfection group was higher than that in the single-transfection groups at 48 h, 60 h, or 72 h after transfection (P<0.01). The apoptotic rate increased to the greatest extent in the co-transfection group relative to any other group (P<0.05). Conclusions: Co-transfection with pSD11-Livin and pSD11-Survivin was more efficient than transfection with either vector alone in reducing the mRNA and protein expression of Livin and Survivin genes in HepG2 cells. Co-transfection also inhibited the proliferation of transfected cells more than the other groups, and induced cellular apoptosis more effectively.

• 생명과학회지
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• 제32권1호
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• pp.23-28
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• 2022

곤충에서 유래한 항균펩타이드 CopA3는 다양한 세포사멸 과정을 차단한다고 알려져 있다. 세균 톡신에 의한 상피세포 세포사멸이나 6-hydroxy dopamine이 야기하는 신경세포 세포사멸 모두를 차단한다. 연구자 등은 최근에 CopA3가 카스파제에 직접 결합하여 그들의 활성형-절단과정을 차단한다고 보고하였다. 하지만 강력한 CopA3의 항세포사멸 효능을 설명하기 위해서는 추가적인 규명이 필요한 실정이다. 본 연구에서는 세포사멸경로의 핵심억제인자인 survivin 발현에 미치는 CopA3의 영향을 확인하였다. 인간 대장상피세포(HT29)에 CopA3를 처리한 뒤 survivin 발현을 추적한 결과, survivin 단백질 양이 유의하게 증가함을 확인하였다. RT-PCR을 통해서 CopA3가 survivin 유전자의 전사를 증가시킴을 확인하였다. 그리고 CopA3 자극이 Sp1 발현을 증가시키는 사실과, Sp1 억제 물질인 tolfenamic acid 처리가 CopA3에 의한 survivin 증가를 차단한다는 결과들을 바탕으로 우리는 CopA3가 Sp1을 통해 survivin 발현을 유도한다는 최종 결론을 도출하였다. 한편 본 연구를 통해서 CopA3의 강력한 항세포사멸 효능을 설명할 수 있는 분자기작을 새롭게 제시하였다고 사려된다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7719-7724
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• 2013

Background: Overexpression of survivin, a known inhibitor of apoptosis, is associated with tumor progression and drug resistance in numerous malignancies, including leukemias. The aim of this study was to investigate the effect of a specific survivin small interference RNA (siRNA) on proliferation and the sensitivity of HL-60 acute myeloid leukemia (AML) cells to the chemotherapeutic drug etoposide. Materials and Methods: The cells were transfected with siRNAs using Lipofectamine $^{TM}2000$ transfection reagent. Relative survivin mRNA and protein levels were measured by quantitative real-time PCR and Western blotting, respectively. Trypan blue exclusion assays were performed to monitor tumor cell proliferation after siRNA transfection. The cytotoxic effects of etoposide and survivin siRNA, alone and in combination, on leukemic cells were determined using MTT assay. Apoptosis was assessed by ELISA cell death assay. Results: Survivin siRNA markedly reduced both mRNA and protein expression levels in a time-dependent manner, leading to distinct inhibition of cell proliferation and increased spontaneous apoptosis. Surprisingly, survivin siRNA synergistically increased the cell toxic effects of etoposide. Moreover, survivin down-regulation significantly enhanced its induction of apoptosis. Conclusions: Our study suggests that down-regulation of survivin by siRNA can trigger apoptosis and overcome drug resistance of leukemia cells. Therefore, survivin siRNA may be an effective adjuvant in AML chemotherapy.

• 대한골관절종양학회지
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• 제11권2호
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• pp.118-125
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• 2005

목적: 골육종에서 세포 사멸과 관련된 survivin, bcl-2, bax 유전자의 발현을 조사하여 임상적 결과와의 연관성에 대해 알아 보고자 하였다. 대상 및 방법: 항암 약물 치료 전 절개 생검으로 얻은 50예의 골육종 조직을 면역조직화학 염색법을 통하여 survivin, bcl-2, bax의 발현을 관찰하였다. 임상적으로 항암 약물 치료에 대한 반응율, 국소재발, 원격전이, 종양학적 결과 등을 연구하여 surviving, bcl-2, bax 유전자 각각의 발현 또는 이들의 복합적인 발현과의 연관성에 대해 통계적으로 분석하였다. 결과: 면역조직화학염색법으로 검사한 survivin 유전자의 발현은 26예(52%)에서 관찰되었고, bcl-2는 23예 (46%), bax는 21예 (42%)에서 관찰되었다. Survivin과 bcl-2의 공동발현은 19예(38%), survivin과 bax의 공동 발현은 13예(26%), bcl-2와 bax의 공동 발현은 8예 (16%), 그리고 이들 3가지 모두의 발현은 총 8예 (16%)에서 관찰되었다. 검사한 3가지 세포 사멸 관련 유전자의 발현과 여러 임상적 변수와의 상관 관계를 조사 하였을 때 조직학적 분류, 나이, 성별, 국소 재발 등과는 유의한 연관성이 없었다. 항암 약물 반응율과 통계적으로 유의한 연관성을 보인 인자는 bcl-2 (P=0.04), 그리고 survivin과 bcl-2가 동시 발현된 경우 (P=0.044)였으며 나쁜 항암 약물 반응율을 나타냈다. 종양학적 결과 중 질병으로 인한 사망과의 연관성을 보인 인자 역시 bcl-2 (P=0.001), 그리고 survivin과 bcl-2가 동시발현된 경우 (P=0.027)였으며, 이들의 발현은 나쁜 종양학적 결과를 나타냈다. Kaplan-Meier 생존율 분석에서 bcl-2 (P=0.0012)의 발현과 survivin, bcl-2의 동시 발현 (P=0.0075)은 생존율과 역의 상관관계를 보였다. 결론: 골육종에서 세포 사멸 관련 유전자의 발현은 비교적 높게 보였으며, bcl-2의 발현은 항암 약물치료에 대한 불량한 반응과 낮은 생존율에 의미 있는 연관성을 보이며, survivin은 bcl-2와 동시에 발현되는 경우에만 이러한 종양학적 결과와 의미 있는 관련이 있었다. 따라서 세포 사멸 관련 유전자들의 면역조직화학염색법을 통한 관찰이 골육종의 예후 판정에 도움이 될 것으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권19호
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• pp.8251-8257
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• 2014

Apoptosis is one of main types of neural cell death and is reversible and is a major target of therapeutic interventions. However, detailed apoptotic cascades still need to be recognized. In present study, we determined the promotion of HIF-$1{\alpha}$ and survivin in brain samples of a mouse model of hypoxic-ischemia and in neuroblastoma SH-SY5Y cells post hypoxia treatment. Then gain-of-function and loss-of-function strategies were adopted to manipulate the HIF-$1{\alpha}$ in SH-SY5Y cells, and hypoxia-induced survivin upregulation and cell apoptosis were determined. Results demonstrated that the HIF-$1{\alpha}$ and survivin were significantly promoted in a mouse model of hypoxic-ischemia or in SH-SY5Y cells post hypoxia in vitro. Manually upregulated HIF-$1{\alpha}$ could promote the hypoxia-induced survivin upregulation and improve the hypoxia-induced SH-SY5Y cell apoptosis. On the other hand, the HIF-$1{\alpha}$ knockdown by RNAi reduced the hypoxia-induced survivin upregulation and cell apoptosis. Therefore, the present study confirmed the protective role of HIF-$1{\alpha}$ and survivin in the hypoxia-induced SH-SY5Y cell apoptosis, and the survivin upregulation by hypoxia is HIF-$1{\alpha}$-dependent. Promotion of HIF-$1{\alpha}$ and survivin might be a valuable stragegy for therapeutic intervention for hypoxic-ischemic encephalopathy.