Ribozyme-mediated attenuation of survivin expression sensitizes human melanoma cells to cisplatin-induced apoptosis

Pennati, Marzia; Colella, Gennaro; Folini, Marco; Citti, Lorenzo; Daidone, Maria Grazia; Zaffaroni, Nadia

doi:10.1172/jci14891

Cited by 66 publications

(64 citation statements)

References 11 publications

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“…In vitro evidences showed that survivin might counteract chemotherapy-induced apoptosis , although univocal data have not been reported (Grossman et al, 2001;Pennati et al, 2002), possibly because of the use of different cell systems or the occurrence of peculiar surviving -cytotoxic drug interactions: for instance, survivin is able to bind polymerised microtubules through a putative tubulin-binding domain in the extended survivin C-terminal a-helix (Verdecia et al, 2000), and counteract paclitaxel-induced apoptosis in NIH3T3 fibroblasts (Li et al, 1998). In clinical studies, Zaffaroni et al (2002) showed that high levels of survivin protein are associated with resistance to regimens containing the microtubule-targeting agent paclitaxel, but are unrelated to cisplatin responsiveness in advanced ovarian cancer.…”

Section: Discussionmentioning

confidence: 99%

Survivin expression in ovarian cancer and its correlation with clinico-pathological, surgical and apoptosis-related parameters

et al. 2005

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We investigated the association of survivin expression with prognosis and other apoptosis-related biological factors in 110 primary ovarian cancer patients admitted to the Division of Gynecologic Oncology, Catholic University of Rome. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded sections by using polyclonal antibody ab469 for survivin, and mouse monoclonal antibodies (clone 124 and DO-7), for bcl-2 and p53, respectively. Cytoplasmic survivin immunoreaction was observed in 84.5% cases, while nuclear survivin immunostaining was observed in 29.1% cases. We failed to find any relationship between cytoplasmic survivin positivity rate and any of the parameters examined. Serous tumours showed a lower percentage of nuclear survivin positivity with respect to other histotypes (20.5 vs 48.6%, respectively; P-value ¼ 0.004). The percentage of nuclear survivin positivity was higher in cases subjected to primary tumour cytoreduction (43.5%), with respect to patients subjected to exploratory laparotomy (20%) (P ¼ 0.024). Bcl-2 and p53 were, respectively, expressed in 27.3 and 60.0% of the cases and their expression was not correlated with survivin status. During the follow-up period, progression and death of disease were observed in 68 (61.8%) and 53 (48.2%) cases, respectively. There was no difference in time to progression and overall survival according to survivin status in ovarian cancer patients. In conclusion, in our experience, the immunohistochemical assessment of survivin status does not seem to be helpful in the prognostic characterisation of ovarian cancer. A more in depth investigation of the complex physiology of divergent survivin variants is needed in order to clarify the biological and the clinical role of differentially located survivin isoforms. (Hoskins et al, 2000), it is conceivable that the assessment of biochemical factors more strictly related to tumour cell biology and intrinsic aggressiveness could help identifying high-risk patients and facilitating management of this disease.Apoptosis (programmed cell death) has been proposed to play a role not only in cancer onset and progression but also in sustaining decreased tumour cell sensitivity to chemotherapy (Hickman, 1992;Thompson, 1995), which still represents one of the main prognostic indicators in this neoplasia (Hoskins et al, 2000). In this context, the analysis of the molecules possibly involved in the modulation of apoptosis seems to be particularly attractive.Survivin is a member of the inhibitors of apoptosis protein (IAP) family, which participates in the complex network regulating programmed cell death and also cell division (Ambrosini et al, 1997;Altieri and Marchisio, 1999;Salvesen and Duckett, 2002). Survivin protein is commonly detected in fetal tissues but not in normal adult tissues, while being overexpressed in human cancer, thus suggesting the contribution of survivin gene reactivation in carcinogenesis (Ambrosini et al, 1997). The crucial role of survivin in protection from apoptosis is supported by the o...

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Section: Discussionmentioning

confidence: 99%

Survivin expression in ovarian cancer and its correlation with clinico-pathological, surgical and apoptosis-related parameters

et al. 2005

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“…Furthermore, clonogenic survival of cells from each line was reduced by 65-86% (Fig 1c, Table 1). By using antisense oligonucleotides, 8,[10][11][12][34][35][36] ribozymes, 9,13,37 and siRNA (in a colon cancer cell line) 23 to knock down expression of survivin mRNA and protein, other investigators have observed a remarkable reduction in survivin mRNA that ranged from 70 to 90% and a reduction in survivin protein that ranged from 60 to 90%. The study conducted by Williams et al 23 has described the application of survivin-specific siRNA, which differs from the construct applied in our study, resulting in a reduction of survivin protein in colon cancer.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of survivin expression by small interfering RNA reduces the clonogenic survival of human sarcoma cell lines independently of p53

et al. 2004

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Survivin, a member of the inhibitors-of-apoptosis gene family, is overexpressed in many tumor types. Survivin is a prognostic marker of soft-tissue sarcomas, but the downregulation of survivin expression and the possible dependency of survivin downregulation on p53 in these tumors have not been investigated. Therefore, we applied small interfering RNA (siRNA) to knock down the expression of survivin in five human sarcoma cell lines with wild-type or mutant p53 alleles. Compared with survivin mRNA expression in the nonsense siRNA-treated sarcoma cell lines, expression after treatment with survivin-specific siRNA was reduced by 73-88%; survivin protein expression was reduced by 52-81%. This finding was coupled with a reduction in clonogenic survival ranging from 65-86%. However, less than 10% of cells treated with survivin-specific siRNA underwent apoptosis. Cell-cycle and morphologic analyses showed that after a dramatic increase in the number of treated cells in the G2/M phase, some of the cells became polyploid; this result indicates that mitosis of a substantial number of treated cells was incomplete. Our findings suggest that survivin-specific siRNA could be a selective treatment to kill sarcoma cells regardless of the presence or absence of wild-type p53 alleles.

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“…1 Attenuation of survivin expression or function by using antisense oligonucleotides, ribozymes, small interfering RNAs (siRNAs), or dominant-negative mutants has been shown to induce apoptosis or mitotic catastrophe in multi types of cancer. [5][6][7][8][9][10] The use of RNA interference (RNAi) has grown at a remarkable rate since the first discovery of RNAi in Caenorhabditis elegans. 11 Subsequently, RNAi was shown to occur in mammalian cells in response to doublestranded siRNAs of B21 nt in length that serve as the effector molecules of sequence-specific gene silencing.…”

Section: Introductionmentioning

confidence: 99%

Survivin knockdown by short hairpin RNA abrogates the growth of human hepatocellular carcinoma xenografts in nude mice

Zhang

Zheng

et al. 2009

Cancer Gene Ther

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Abnormal high activation of survivin is involved in carcinogenesis of various types of cancer. Survivin has been shown to promote cell proliferation in human hepatocellular carcinoma (HCC). Survivin-targeting approaches have become a promising strategy for treating HCC. Here, we used a reporter system to screen effective survivin siRNA sequences. The effect of vector-based survivin short hairpin RNA (shRNA) on the malignant phenotype of HCC cells in vitro and in vivo was determined, and an adenovirusmediated shRNA expression vector was developed to decrease survivin expression of the established HCC tumor in nude mice. In vitro study showed that stable survivin knockdown inhibited cancer cell proliferation, enhanced apoptotic susceptibility, arrested cell cycle in the G1 phase and resulted in apparent mitotic catastrophe. Moreover, cells stably expressing survivin shRNA showed decreased tumorigenicity in nude mice. An additional in vivo study showed that intratumoral injection of adenovirus-delivered survivin shRNA suppressed tumor growth by spontaneous apoptosis of cancer cells and significantly prolonged animal survival. In conclusion, we proved the therapeutic potential of survivin shRNA for the treatment of HCC. And our results indicated that adenovirus-delivered shRNA may serve as a novel therapeutic for HCC.

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Ribozyme-mediated attenuation of survivin expression sensitizes human melanoma cells to cisplatin-induced apoptosis

Cited by 66 publications

References 11 publications

Survivin expression in ovarian cancer and its correlation with clinico-pathological, surgical and apoptosis-related parameters

Survivin expression in ovarian cancer and its correlation with clinico-pathological, surgical and apoptosis-related parameters

Knockdown of survivin expression by small interfering RNA reduces the clonogenic survival of human sarcoma cell lines independently of p53

Survivin knockdown by short hairpin RNA abrogates the growth of human hepatocellular carcinoma xenografts in nude mice

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