hTERT-siRNA Could Potentiate the Cytotoxic Effect of Gemcitabine to Pancreatic Cancer Cells Bxpc-3

Tan, Jing; Zhou, Xin; Hong, Zhu

doi:10.6002/ect.2011.0157

Cited by 2 publications

(3 citation statements)

References 19 publications

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“…In this regard, a number of TERT silencing approaches proved beneficial in tumor regression. Evidently, knockdown of hTERT with siRNA suppresses the growth of PC cells via Bcl2 inhibition [55] and potentiate chemotherapy [56]. In addition, voluminous evidence implicate EGFR [57]–[60], AKT [ 61 ]–[ 64 ], AurKβ, STAT3 [65]–[68], PDGFA [69], [70], VEGF [71]–[73] and FGF [74]–[77] in pancreatic carcinogenesis, progression/metastasis and are comprehended as potential molecular targets to mitigate the disease.…”

Section: Discussionmentioning

confidence: 99%

Anti-Pancreatic Cancer Deliverables from Sea: First-Hand Evidence on the Efficacy, Molecular Targets and Mode of Action for Multifarious Polyphenols from Five Different Brown-Algae

et al. 2013

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Pancreatic cancer (PC) remains the fourth leading cause of cancer death with an unacceptable survival that has remained relatively unchanged over the past 25 years. The presence of occult or clinical metastases at the time of diagnosis together with the lack of effective chemotherapies pose a dire need for designing new and targeted therapeutic deliverables that favors the clinical outcome. Herein, we investigated the anti-tumorigenic potential of polyphenols from five different brown-algae in human PC cells (MiaPaCa-2, Panc-1, BXPC-3 and Panc-3.27). Total anti-oxidant capacity (TAC) analysis on stepwise polyphenol separations with increasing polarity (Hexane-DCM-EA-methanol) identified high levels of TAC in DCM and EA extractions across all seaweeds assessed. All DCM and EA separated polyphenols induced a dose-dependent and sustained (time-independent) inhibition of cell proliferation and viability. Further, these polyphenols profoundly enhanced DNA damage (acridine orange/Ethidium bromide staining and DNA fragmentation) in all the cell lines investigated. More importantly, luciferase reporter assay revealed a significant inhibition of NFκB transcription in cells treated with polyphenols. Interestingly, QPCR analysis identified a differential yet definite regulation of pro-tumorigenic EGFR, VEGFA, AKT, hTERT, kRas, Bcl2, FGFα and PDGFα transcription in cells treated with DCM and EA polyphenols. Immunoblotting validates the inhibitory potential of seaweed polyphenols in EGFR phosphorylation, kRas, AurKβ and Stat3. Together, these data suggest that intermediate polarity based fractions of seaweed polyphenols may significantly potentiate tumor cell killing and may serve as potential drug deliverable for PC cure. More Studies dissecting out the active constituents in potent fractions, mechanisms of action and synergism, if any, are warranted and are currently in process.

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Section: Discussionmentioning

confidence: 99%

Anti-Pancreatic Cancer Deliverables from Sea: First-Hand Evidence on the Efficacy, Molecular Targets and Mode of Action for Multifarious Polyphenols from Five Different Brown-Algae

et al. 2013

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“…Apoptosis stimulation Cell cycle arrest at G0/G1 phase Enhancing GEM sensitivity [188] In vitro MiaPaCa2 cells HIF-1α…”

Section: In Vitro Bxpc3 Cells Htertmentioning

confidence: 99%

“…The hTERT-siRNA can increase the number of PC cells undergoing apoptosis. The hTERT down-regulation induces cell cycle arrest at G0/G1 phase and enhances number of PC cells in S and G2/M phases [ 188 ]. Following hTERT down-regulation by siRNA, expressions of Bcl-2 and COX-2, as tumor-promoting factors undergo inhibition that is of importance for inducing apoptosis in PC cells [ 189 ], and enhancing their sensitivity to chemotherapy.…”

Section: Sirna and Pancreatic Cancer Therapymentioning

confidence: 99%

Pre-Clinical and Clinical Applications of Small Interfering RNAs (siRNA) and Co-Delivery Systems for Pancreatic Cancer Therapy

Mirzaei

Gholami

Ang

et al. 2021

Cells

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Pancreatic cancer (PC) is one of the leading causes of death and is the fourth most malignant tumor in men. The epigenetic and genetic alterations appear to be responsible for development of PC. Small interfering RNA (siRNA) is a powerful genetic tool that can bind to its target and reduces expression level of a specific gene. The various critical genes involved in PC progression can be effectively targeted using diverse siRNAs. Moreover, siRNAs can enhance efficacy of chemotherapy and radiotherapy in inhibiting PC progression. However, siRNAs suffer from different off target effects and their degradation by enzymes in serum can diminish their potential in gene silencing. Loading siRNAs on nanoparticles can effectively protect them against degradation and can inhibit off target actions by facilitating targeted delivery. This leads to enhanced efficacy of siRNAs in PC therapy. Moreover, different kinds of nanoparticles such as polymeric nanoparticles, lipid nanoparticles and metal nanostructures have been applied for optimal delivery of siRNAs that are discussed in this article. This review also reveals that how naked siRNAs and their delivery systems can be exploited in treatment of PC and as siRNAs are currently being applied in clinical trials, significant progress can be made by translating the current findings into the clinical settings.

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hTERT-siRNA Could Potentiate the Cytotoxic Effect of Gemcitabine to Pancreatic Cancer Cells Bxpc-3

Abstract: Objectives: This study sought to observe transfection of pancreatic cancer cells BxPC-3 with recombinant plasmid pSilencer4.1-cytomegalovirus neo-hTERT-siRNA and examine the combined effect of gemcitabine and siRNA inhibition of telomerase on pancreatic cancer cells.

Cited by 2 publications

References 19 publications

Anti-Pancreatic Cancer Deliverables from Sea: First-Hand Evidence on the Efficacy, Molecular Targets and Mode of Action for Multifarious Polyphenols from Five Different Brown-Algae

Anti-Pancreatic Cancer Deliverables from Sea: First-Hand Evidence on the Efficacy, Molecular Targets and Mode of Action for Multifarious Polyphenols from Five Different Brown-Algae

Pre-Clinical and Clinical Applications of Small Interfering RNAs (siRNA) and Co-Delivery Systems for Pancreatic Cancer Therapy

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