203 Sirna-mediated down-regulation of survivin inhibits bladder cancer cell growth

Ning, Shuangli; Fuessel, Susanne; Kotzsch, Matthias; Kraemer, Kai; Kappler, Matthias; Schmidt, Frank; Täubert, Helge; Wirth, Manfred P.; Meye, Axel

doi:10.1016/s1569-9056(04)90204-7

Cited by 34 publications

(47 citation statements)

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“…Survivin, a member of the inhibitor of apoptosis (IAP) family, is abundantly expressed in the G2/M phase of the cell cycle to regulate mitosis (40). Downregulation of survivin by siRNA inhibited bladder cancer growth with G2/M phase arrest (41). However, survivin inhibitor YM155 caused variable cell cycle arrest and even a lack of changes in cell cycles were found in previous reports.…”

Section: Discussionmentioning

confidence: 93%

Therapeutic potential of sepantronium bromide YM155 in gemcitabine-resistant human urothelial carcinoma cells

et al. 2013

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Abstract. Survivin is overexpressed in transitional cell carcinoma (TCC), the most common type of bladder cancer. Previous reports demonstrated that knockdown of survivin by siRNA induced apoptosis of TCC cells. The present study evaluated the therapeutic effects of sepantronium bromide (YM155), a novel small molecule survivin inhibitor under clinical trials, on TCC cells in vitro. BFTC905, a grade III TCC cell line derived from a patient of blackfoot disease in Taiwan, was the most gemcitabine-resistant cell line when compared to BFTC909, TSGH8301 and T24 in cytotoxicity assay, resulting from upregulation of securin and bcl-2 after gemcitabine treatment. YM155 caused potent concentration-dependent cytotoxicity in 4 TCC cell lines (IC 50 s ≤20 nM), but exhibited no cytotoxicity in survivin-null primary human urothelial cells. For BFTC905 cells, addition of gemcitabine and/or cisplatin, the standard TCC chemotherapy regimen, to YM155 did not exert additive cytotoxic effects. Molecular analyses indicated that YM155 inhibited the proliferation of BFTC905 cells by increasing p27 kip1 , suppressing Ki-67, and inducing quiescence. In addition, YM155 elicited apoptosis manifested with DNA fragmentation through suppressing the expression of survivin, securin and bcl-2. Furthermore, YM155 induced autophagy in BFTC905 cells as autophagic inhibitor, 3-methyladenine, attenuated YM155-induced LC3B-II levels and reversed the cytotoxicity of YM155. mTOR inhibitors sirolimus and everolimus did not increase YM155-induced expression of LC3B-II nor augment YM155-induced cytotoxicity. These results indicate that YM155 exerts its lethal effect on BFTC905 cells via apoptotic and autophagic death pathways and suggest that YM155 may be a potential drug for the therapy of gemcitabine-resistant bladder cancer.

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Section: Discussionmentioning

confidence: 93%

Therapeutic potential of sepantronium bromide YM155 in gemcitabine-resistant human urothelial carcinoma cells

et al. 2013

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“…The human BCa cell line 5637, which has been reported to have moderate expression of survivin [7,8,19] , was used in our previous study [7,8] and in the present investigation. The laser scanning confocal fluorescence microscopy images (Figure 3) show that the emission at 560±20 nm (the Cy3 acceptor fluorescence emission wavelength) results in a stronger fluorescence signal than the emission at 520±20 nm (the FAM donor fluorescence emission wavelength), indicating the excellent specificity of the dual FRET MBs.…”

Section: Discussionmentioning

confidence: 99%

Specific survivin dual fluorescence resonance energy transfer molecular beacons for detection of human bladder cancer cells

et al. 2011

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Aim: Survivin molecular beacons can be used to detect bladder cancer cells in urine samples non-invasively. The aim of this study is to improve the specificity of detection of bladder cancer cells using survivin dual fluorescence resonance energy transfer molecular beacons (FRET MBs) that have fluorophores forming one donor-acceptor pair. Methods: Survivin-targeting dual fluorescence resonance energy transfer molecular beacons with unique target sequences were designed, which had no overlap with the other genes in the apoptosis inhibitor protein family. Human bladder cancer cell lines 5637, 253J and T24, as well as the exfoliated cells in the urine of healthy adults and patients with bladder cancer were examined. Images of cells were taken using a laser scanning confocal fluorescence microscope. For assays using dual FRET MBs, the excitation wavelength was 488 nm, and the emission detection wavelengths were 520±20 nm and 560±20 nm, respectively. npg cellular delivery and thus has been hard to popularize in clinical practice [11] . In our previous study, we showed that fixing cells with ice-cold acetone was a simple, effective method to use with MBs [8,12] . In this study, we aimed to use this simple method to determine whether dual FRET MBs could be used to detect survivin mRNA in BCa cells, which might lay the foundation for clinical applications.

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“…We then studied the cell cycle following survivin down-regulation (1,15,18,38,39) for the oligonucleotides described here. To this point, only ISIS23722 has been noted to confer cell cycle arrest (in G 2 -M; ref.…”

Section: Cell Cycle Arrestmentioning

confidence: 99%

SPC3042: a proapoptotic survivin inhibitor

Hansen¹,

Fisker²,

Westergaard³

et al. 2008

Molecular Cancer Therapeutics

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The ability to regulate the cellular homeostasis of a higher organism through tight control of apoptosis and cell division is crucial for life. Dysregulation of these mechanisms is often associated with cancerous phenotypes in cells. Optimal cancer therapy is a fine balance between effective cancer cell killing and at the same time minimizing, or avoiding, damage to the surrounding healthy tissue. To obtain this, it is necessary to identify and inhibit molecular targets on which the cancer cells are strongly dependent. Survivin represents such a target, and it has been published previously that peptide vaccines, the small-molecule YM155, and the antisense molecule LY2181308/ISIS23722, via different mechanisms, have been used as survivin inhibitors. In this article, a new potent antisense inhibitor of survivin, SPC3042, is presented, and the properties of SPC3042 are compared with the previously published antisense drug, LY2181308/ ISIS23722. SPC3042 is a 16-mer locked nucleic acid (LNA) oligonucleotide and designed as a fully phosphorothiolated gapmer containing 7 LNA nucleotides in the flanks. The LNA nucleotides in SPC3042 provide nuclease stability and higher potency for survivin mRNA inhibition compared with earlier generations of antisense reagents. It is shown that the down-regulation of survivin with SPC3042 leads to cell cycle arrest, pronounced cellular apoptosis, and down-regulation of Bcl-2. It is also shown that SPC3042 is a sensitizer of prostate cancer cells to Taxol treatment in vitro and in vivo. [Mol Cancer Ther 2008;7(9):2736 -45]

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203 Sirna-mediated down-regulation of survivin inhibits bladder cancer cell growth

Cited by 34 publications

References 0 publications

Therapeutic potential of sepantronium bromide YM155 in gemcitabine-resistant human urothelial carcinoma cells

Therapeutic potential of sepantronium bromide YM155 in gemcitabine-resistant human urothelial carcinoma cells

Specific survivin dual fluorescence resonance energy transfer molecular beacons for detection of human bladder cancer cells

SPC3042: a proapoptotic survivin inhibitor

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