Application of combination of short hairpin RNA segments for silencing VEGF, TERT, and Bcl-xl expression in laryngeal squamous carcinoma

Wang, Yan; Tao, Zezhang; Chen, Shi‐Ming; Xiao, Bokui; Zhou, Xuhong; Liu, Junping

doi:10.4161/cbt.7.6.5910

Cited by 16 publications

(15 citation statements)

References 18 publications

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“…19 Hong et al 20 have found that simultaneous C-myc and stat3 gene silencing is better than single C-myc or stat3 gene silencing in inhibiting growth and proliferation of melanoma cella. Yan Wang et al 21 has found that three-gene silencing is better than single gene silencing in inhibiting Hep-2 cell growth and proliferation, which is consistent with our results. In this study, reverse transcriptase PCR and western blotting indicated that mRNA and protein of the four genes were all decreased after simultaneous four-gene silencing, demonstrating that constructed plasmids can simultaneously inhibit the four target genes.…”

Section: Discussionsupporting

confidence: 93%

Effects of RNA interference targeting four different genes on the growth and proliferation of nasopharyngeal carcinoma CNE-2Z cells

Song

2011

Cancer Gene Ther

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To explore the effects of RNA interference targeting four different genes (VEGF, C-myc, Survivin, hTERT) on the growth and proliferation of nasopharyngeal carcinoma (NPC) CNE-2Z cells. Fluorescein-labeled short-hairpin (sh)RNA plasmids together and separately targeting VEGF, C-myc, Survivin and hTERT were built and respectively called plasmid-shVEGF-shC-myc-shSurvivinshhTERT, plasmid-shVEGF, plasmid-shC-myc, plasmid-shSurvivin, plasmid-shhTERT. These plasmids were respectively transfected into human NPC CNE-2Z cells and xenograft tumors in nude mice. The expression of plasmids in NPC CNE-2Z cells and xenograft tumors was observed. Cell proliferation was detected with MTT assay. The mRNA and protein expression were determined by real-time PCR and western blot, respectively. The effects of plasmids on the biological behavior of CNE-2Z cells were observed with transwell invision chamber models. Apoptosis was determined with flow cytometer. The inhibitory effect of plasmids on xenograft tumors was observed in nude mice. The plasmid containing four different shRNAs could significantly inhibit CNE-2Z cell proliferation and decrease invasion ability in vitro compared with plasmids with each single shRNA (Po0.05). The plasmid containing four different shRNAs could simultaneously downregulate VEGF, C-myc, surviving, hTERT mRNA and protein expression in the CNE-2Z cells. The multiple gene shRNA could more significantly induce cell apoptosis than each single shRNA, respectively (Po0.05). The combinative silencing of these four genes had a better inhibitory effect on xenograft tumors than the silencing of each single shRNA (Po0.05). RNA interference targeting multiple genes can effectively inhibit NPC proliferation and induce apoptosis, which provides an experiment basis for NPC gene therapy.

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Section: Discussionsupporting

confidence: 93%

Effects of RNA interference targeting four different genes on the growth and proliferation of nasopharyngeal carcinoma CNE-2Z cells

Song

2011

Cancer Gene Ther

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“…In addition, the ratios of liver cancer cell growth inhibition and apoptosis in the β-catenin and STAT3 co-transfection group were significantly greater than those in the groups transfected with β-catenin or STAT3 siRNA alone. Similar to the results of the present study, simultaneous silencing of vascular endothelial growth factor, telomerase reverse transcriptase and Bcl-extra large expression improved the inhibition of cell growth and promotion of apoptosis in laryngeal squamous carcinoma (30).…”

Section: Discussionsupporting

confidence: 79%

“…Inhibiting the functions of the key genes of several pathways together is expected to achieve improved results for the purpose of cancer therapy (30). In agreement with this hypothesis, it was demonstrated that silencing β-catenin and STAT3 genes together led to enhanced cell apoptosis and loss of cell viability of HCC cells as compared with silencing of β-catenin and STAT3 genes individually.…”

Section: Discussionsupporting

confidence: 70%

Simultaneous silencing of β-catenin and signal transducer and activator of transcription 3 synergistically induces apoptosis and inhibits cell proliferation in HepG2 liver cancer cells

Wang

Liu

Huang

et al. 2015

Molecular Medicine Reports

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Abstract. The tumorigenesis and maintenance of a cancer cells is dependent upon the collaboration of multiple signaling pathways. Signal transducer and activator of transcription 3 (STAT3) and β-catenin are at the center of multiple cancer-associated signaling pathways; therefore, simultaneously targeting STAT3 and β-catenin may be a potential cancer treatment, leading to induced lethality of cancer cells. In the present study, HepG 2 liver cancer cells were transfected with small interfering RNA (siRNA) against β-catenin and STAT3 alone or in combination. The cell growth was assessed using an MTT assay and the levels of cell apoptosis were detected using flow cytometry. Protein levels of caspase-3, cleaved caspase-3, poly(ADP-ribose) polymerase (PARP) and cleaved PARP were determined using western blot analysis. Following siRNA transfection, β-catenin and STAT3 protein levels decreased at 72 h. HepG 2 cell growth inhibition and early apoptosis in the β-catenin and STAT3 siRNA co-transfection group were significantly greater than those in the groups transfected with β-catenin or STAT3 siRNA alone. Decreased caspase-3 and PARP levels, as well as enhanced cleavage of caspase-3 and PARP were observed in the β-catenin and STAT3 co-transfection group. Simultaneous silencing of β-catenin and STAT3 using siRNAs resulted in an enhanced loss of cell viability and induction of apoptosis in HepG 2 liver cancer cells, suggesting that these genes are promising targets for the further preclinical and clinical development of anti-cancer therapeutic strategies, which target several cancer signaling pathways simultaneously.

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“…As knockdown of Tert or Terc significantly reduces tumor growth,37,38 telomerase-targeting drugs may be an alternative to drugs that target telomeres.…”

Section: Drugs Targeting Telomerasementioning

confidence: 99%

Clinical implications of antitelomeric drugs with respect to the nontelomeric functions of telomerase in cancer

Roh

Sung

Lee³

2013

OTT

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Telomerase is responsible for maintaining the length of telomeres at the ends of chromosomes. Although most somatic cells do not exhibit telomerase activity, it is reactivated in approximately 85% of cancers. This simple and attractive phenomenon steers the development of anticancer drugs targeting telomeres and telomerase. Recent studies have been revealing extratelomeric roles of telomerase in normal tissues, affecting processes that are critical for survival and aging of organisms. In this review, we will discuss the current therapeutic strategies targeting telomeres and telomerase and evaluate their potential advantages and risks with respect to nontelomeric functions.

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Application of combination of short hairpin RNA segments for silencing VEGF, TERT, and Bcl-xl expression in laryngeal squamous carcinoma

Cited by 16 publications

References 18 publications

Effects of RNA interference targeting four different genes on the growth and proliferation of nasopharyngeal carcinoma CNE-2Z cells

Effects of RNA interference targeting four different genes on the growth and proliferation of nasopharyngeal carcinoma CNE-2Z cells

Simultaneous silencing of β-catenin and signal transducer and activator of transcription 3 synergistically induces apoptosis and inhibits cell proliferation in HepG2 liver cancer cells

Clinical implications of antitelomeric drugs with respect to the nontelomeric functions of telomerase in cancer

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