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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

The proliferation, migration and invasiveness of NSCLC cells infected with SIRT 1 siRNA and control siRNA.a. the SRIT1 expression after SIRT1 si-RNA transfection in H292 cells. b the absorbance at 562nm between cells infected with SIRT 1 si-RNA and control si-RNA (P<0.001). c the cell numbers of migrated cells infected with SIRT 1 si-RNA and control si-RNA (P<0.001). d the cell numbers of invasive cells infected with SIRT 1 si-RNA and control si-RNA (P<0.001).
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pone-0079162-g003: The proliferation, migration and invasiveness of NSCLC cells infected with SIRT 1 siRNA and control siRNA.a. the SRIT1 expression after SIRT1 si-RNA transfection in H292 cells. b the absorbance at 562nm between cells infected with SIRT 1 si-RNA and control si-RNA (P<0.001). c the cell numbers of migrated cells infected with SIRT 1 si-RNA and control si-RNA (P<0.001). d the cell numbers of invasive cells infected with SIRT 1 si-RNA and control si-RNA (P<0.001).

Mentions: Western blot results showed that the SIRT 1 protein expressions in H292 cells were significantly inhibited by SIRT1 si-RNA silencing technique (Figure 3a). The cell proliferation assays revealed the cell growth rate was significantly inhibited in H292 cells after SIRT1 si-RNA transfection by 47.3% compared to cells treated with control si-RNA (Figure 3ba). Cell migration assay showed that SIRT1 knockdown significantly decreased the migrated cell numbers by 43.8% (Figure 3c). Furthermore, silencing of SIRT1 gene dramatically inhibited the invasive ability of H292 cells by 57.6% (Figure 3d).


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)

The proliferation, migration and invasiveness of NSCLC cells infected with SIRT 1 siRNA and control siRNA.a. the SRIT1 expression after SIRT1 si-RNA transfection in H292 cells. b the absorbance at 562nm between cells infected with SIRT 1 si-RNA and control si-RNA (P<0.001). c the cell numbers of migrated cells infected with SIRT 1 si-RNA and control si-RNA (P<0.001). d the cell numbers of invasive cells infected with SIRT 1 si-RNA and control si-RNA (P<0.001).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0079162-g003: The proliferation, migration and invasiveness of NSCLC cells infected with SIRT 1 siRNA and control siRNA.a. the SRIT1 expression after SIRT1 si-RNA transfection in H292 cells. b the absorbance at 562nm between cells infected with SIRT 1 si-RNA and control si-RNA (P<0.001). c the cell numbers of migrated cells infected with SIRT 1 si-RNA and control si-RNA (P<0.001). d the cell numbers of invasive cells infected with SIRT 1 si-RNA and control si-RNA (P<0.001).
Mentions: Western blot results showed that the SIRT 1 protein expressions in H292 cells were significantly inhibited by SIRT1 si-RNA silencing technique (Figure 3a). The cell proliferation assays revealed the cell growth rate was significantly inhibited in H292 cells after SIRT1 si-RNA transfection by 47.3% compared to cells treated with control si-RNA (Figure 3ba). Cell migration assay showed that SIRT1 knockdown significantly decreased the migrated cell numbers by 43.8% (Figure 3c). Furthermore, silencing of SIRT1 gene dramatically inhibited the invasive ability of H292 cells by 57.6% (Figure 3d).

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