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Journal ArticleDOI

An Antisense Plasmid Targeting Survivin Expression Induces Apoptosis and Sensitizes Hepatocarcinoma Cells to Chemotherapy

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TLDR
The threshold of apoptosis was decreased after survivin was silenced, and the sensitivity to chemotherapy was increased, suggesting the existence of a potential new target for gene therapy.
Abstract
To explore the change of sensitivity to chemotherapy of antisense RNA targeting survivin on hepatocarcinoma carcinoma cellsin vitro. Survivin mRNA structure region was amplified by RT-PCR and inserted inversely into eukaryotic expression vector pcDNA3. The antisense expression plasmid pcDNA3/survivin was transfected into HepG2 with lipofectAMINETM, 2000 (FL2000), with low concentration of 5-fluorouracil (5-Fu) added. Survivin protein was detected by westernblot, the growth activity was measured by MTT, and apoptosis was detected by Flow cytometry 12 h, 24 h, 48 h after transfection. The activity of caspase-3 was found by quantitative assay 48 h after transfection. The construction of antisense RNA vector pcDNA3/survivin was verified by restricted endonuclease digestion and nucleotide sequencing. Compared with normal group, 5-Fu and antisense survivin group, the cells growth inhibition, apoptosis index, and caspase-3 activity were increased in antisense survivin transfected + 5-Fu group. The threshold of apoptosis was decreased after survivin was silenced, and the sensitivity to chemotherapy was increased. These findings suggest the existence of a potential new target for gene therapy.

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Survivin expression in breast cancer predicts clinical outcome and is associated with HER2, VEGF, urokinase plasminogen activator and PAI-1

TL;DR: The independent prognostic relevance of survivin, when combined with previous data from model systems implicating survivin in the inhibition of apoptosis, suggests that survivin may be a suitable target for future therapeutic strategies.
Journal ArticleDOI

Survivin expression and targeting in breast cancer.

TL;DR: Survivin is over expressed in majority of breast cancers and the over expression of survivin is found to correlate with HER 2 and EGFR expression, and has been found to confer resistance to chemotherapy and radiation.
Journal ArticleDOI

Characterization of cell death events induced by anti-neoplastic drugs cisplatin, paclitaxel and 5-fluorouracil on human hepatoma cell lines: Possible mechanisms of cell resistance.

TL;DR: Three drugs tested in this study could induce cell death, with paclitaxel being more effective inducing apoptosis, and 5FU was only effective at high doses and its mechanism seems to be primarily related to necrosis in Hep3B and probably apoptosis in HepG2.
Journal ArticleDOI

Sensitization of osteosarcoma cell line SaOS-2 to chemotherapy by downregulating survivin.

TL;DR: It is found that the downregulation of survivin by pSUPER-sh could enhance the anticancer effects of chemotherapies such as etoposide, cisplatin and doxorubicin through decreasing mitochondrial membrane potentials and increasing caspase-3 activity.
References
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Journal ArticleDOI

Caspases: Enemies Within

TL;DR: This work has shown that understanding caspase regulation is intimately linked to the ability to rationally manipulate apoptosis for therapeutic gain.
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A novel anti-apoptosis gene, survivin , expressed in cancer and lymphoma

TL;DR: It is suggested that apoptosis inhibition may be a general feature of neoplasia and survivin is identified as a potential new target for apoptosis-based therapy in cancer and lymphoma.
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X-linked IAP is a direct inhibitor of cell-death proteases

TL;DR: It is shown that human X-chromosome-linked IAP directly inhibits at least two members of the caspase family of cell-death proteases, caspasing-3 and caspases-7, providing evidence for a mechanism of action for these mammalian cell- death suppressors.
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The c‐IAP‐1 and c‐IAP‐2 proteins are direct inhibitors of specific caspases

TL;DR: Three of the known members of the human IAP family are investigated, suggesting that c‐IAP‐1 and c‐ IAP‐2 function similarly to XIAP by inhibiting the distal cell death proteases, caspases‐3 and ‐7, whereas NAIP presumably inhibits apoptosis via other targets.
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The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins

TL;DR: The biochemical purification and subsequent molecular cloning of two novel TNFR2-associated proteins, designated c-IAP1 and c- IAP2, that are closely related mammalian members of the inhibitor of apoptosis protein (IAP) family originally identified in baculoviruses are reported.
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