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SIRT1 expression is associated with the chemotherapy response and prognosis of patients with advanced NSCLC.

Zhang T, Rong N, Chen J, Zou C, Jing H, Zhu X, Zhang W - PLoS ONE (2013)

Bottom Line: We found that the SIRT1 expressions were significantly associated with the tumor stage, tumor size and differentiation status.In vitro studies revealed that the reduced expression SIRT 1 by siRNA technique significantly inhibited cell proliferation, migration and invasion.The in vivo tumorgenesis and metastasis assays showed that SIRT1 knockdown dramatically reduced the tumor volume and the metastatic ability in nude mice.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiovascular Surgery, Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong Province, China.

ABSTRACT

Aim: The role of Sirtuin 1 (SIRT 1) in carcinogenesis is controversial. This study was to explore the association between the SIRT1 expression and the clinical characteristics, the responsiveness to chemotherapy and prognosis in Non-small cell lung cancer (NSCLC).

Methods: We enrolled 295 patients with inoperable advanced stage of NSCLC, namely, stage III (A+B) and IV NSCLC. All patients had received platinum-based chemotherapy after diagnosis and the chemotherapy response were evaluated. All patients were followed up for overall survival (OS) and progression free survival (PFS). In vitro, H292 cells were tranfected with SIRT1 small interfering RNA (siRNA). The cell biological behaviors and chemosensitivity to cisplatin treatment were studied. The in vivo tumorgenesis and metastasis assays were performed in nude mice.

Results: We found that the SIRT1 expressions were significantly associated with the tumor stage, tumor size and differentiation status. Patients with high SIRT 1 expressions had a significantly higher chance to be resistant to chemotherapy than those with low SIRT 1 expression. Patients with high expression of SIRT1 had significantly shorter OS and DFS than those with low expression. Cox analyses confirmed that the SIRT 1 expression was a strong predictor for a poor OS and PFS in NSCLC patients underwent Platinum-based chemotherapy. In vitro studies revealed that the reduced expression SIRT 1 by siRNA technique significantly inhibited cell proliferation, migration and invasion. More importantly, SIRT1 si-RNA significantly enhanced the chemosensitivity of H292 cells to cisplatin treatment. The in vivo tumorgenesis and metastasis assays showed that SIRT1 knockdown dramatically reduced the tumor volume and the metastatic ability in nude mice.

Conclusion: Collectively, our data suggest that the SIRT1 expression may be a molecular marker associated with the NSLCLC clinical features, treatment responsiveness and prognosis of advanced NSCLC.

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Related in: MedlinePlus

SIRT 1 siRNA-induced enhancement of chemosensitivity to cisplatin.Sensitivity curves of the H292 cell line toward cisplatin via MTT assay. Growth inhibition of SIRT1 siRNA-transfected cells was observed after exposure to different concentrations of cisplatin (0-8ug/mL).
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pone-0079162-g004: SIRT 1 siRNA-induced enhancement of chemosensitivity to cisplatin.Sensitivity curves of the H292 cell line toward cisplatin via MTT assay. Growth inhibition of SIRT1 siRNA-transfected cells was observed after exposure to different concentrations of cisplatin (0-8ug/mL).

Mentions: Exposure of SIRT1 si-RNA-transfected H292 cells to different concentrations of cisplatin induced significant proliferative inhibition. When the concentration of cisplatin was 8 ug/ml; the viability of SIRT1 siRNA-transfected cells showed no significant difference compared with those of the control siRNA-transfected and untreated cells (Figure 4). Meanwhile, the IC50 concentration of cisplatin for cancer cells decreased significantly from 6.34 ug/ml in control cells and 1.61 ug/ml in SIRT1 si-RNA-transfected cells, indicating that SIRT1 silencing significantly enhanced the chemosensitivity of H292 cells to cisplatin treatment.


SIRT1 expression is associated with the chemotherapy response and prognosis of patients with advanced NSCLC.

Zhang T, Rong N, Chen J, Zou C, Jing H, Zhu X, Zhang W - PLoS ONE (2013)

SIRT 1 siRNA-induced enhancement of chemosensitivity to cisplatin.Sensitivity curves of the H292 cell line toward cisplatin via MTT assay. Growth inhibition of SIRT1 siRNA-transfected cells was observed after exposure to different concentrations of cisplatin (0-8ug/mL).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3818418&req=5

pone-0079162-g004: SIRT 1 siRNA-induced enhancement of chemosensitivity to cisplatin.Sensitivity curves of the H292 cell line toward cisplatin via MTT assay. Growth inhibition of SIRT1 siRNA-transfected cells was observed after exposure to different concentrations of cisplatin (0-8ug/mL).
Mentions: Exposure of SIRT1 si-RNA-transfected H292 cells to different concentrations of cisplatin induced significant proliferative inhibition. When the concentration of cisplatin was 8 ug/ml; the viability of SIRT1 siRNA-transfected cells showed no significant difference compared with those of the control siRNA-transfected and untreated cells (Figure 4). Meanwhile, the IC50 concentration of cisplatin for cancer cells decreased significantly from 6.34 ug/ml in control cells and 1.61 ug/ml in SIRT1 si-RNA-transfected cells, indicating that SIRT1 silencing significantly enhanced the chemosensitivity of H292 cells to cisplatin treatment.

Bottom Line: We found that the SIRT1 expressions were significantly associated with the tumor stage, tumor size and differentiation status.In vitro studies revealed that the reduced expression SIRT 1 by siRNA technique significantly inhibited cell proliferation, migration and invasion.The in vivo tumorgenesis and metastasis assays showed that SIRT1 knockdown dramatically reduced the tumor volume and the metastatic ability in nude mice.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiovascular Surgery, Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong Province, China.

ABSTRACT

Aim: The role of Sirtuin 1 (SIRT 1) in carcinogenesis is controversial. This study was to explore the association between the SIRT1 expression and the clinical characteristics, the responsiveness to chemotherapy and prognosis in Non-small cell lung cancer (NSCLC).

Methods: We enrolled 295 patients with inoperable advanced stage of NSCLC, namely, stage III (A+B) and IV NSCLC. All patients had received platinum-based chemotherapy after diagnosis and the chemotherapy response were evaluated. All patients were followed up for overall survival (OS) and progression free survival (PFS). In vitro, H292 cells were tranfected with SIRT1 small interfering RNA (siRNA). The cell biological behaviors and chemosensitivity to cisplatin treatment were studied. The in vivo tumorgenesis and metastasis assays were performed in nude mice.

Results: We found that the SIRT1 expressions were significantly associated with the tumor stage, tumor size and differentiation status. Patients with high SIRT 1 expressions had a significantly higher chance to be resistant to chemotherapy than those with low SIRT 1 expression. Patients with high expression of SIRT1 had significantly shorter OS and DFS than those with low expression. Cox analyses confirmed that the SIRT 1 expression was a strong predictor for a poor OS and PFS in NSCLC patients underwent Platinum-based chemotherapy. In vitro studies revealed that the reduced expression SIRT 1 by siRNA technique significantly inhibited cell proliferation, migration and invasion. More importantly, SIRT1 si-RNA significantly enhanced the chemosensitivity of H292 cells to cisplatin treatment. The in vivo tumorgenesis and metastasis assays showed that SIRT1 knockdown dramatically reduced the tumor volume and the metastatic ability in nude mice.

Conclusion: Collectively, our data suggest that the SIRT1 expression may be a molecular marker associated with the NSLCLC clinical features, treatment responsiveness and prognosis of advanced NSCLC.

Show MeSH
Related in: MedlinePlus