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Silencing of insulin-like growth factor-1 receptor enhances the radiation sensitivity of human esophageal squamous cell carcinoma in vitro and in vivo.

Zhao H, Gu X - World J Surg Oncol (2014)

Bottom Line: Eca-109 and TE-1 cells were transfected with 100 nM IGF-1r siRNA, and a combination of IGF-1r siRNA and radiation therapy was tested in vitro and in vivo.The effects of IGF-1r siRNA were determined through Western blotting and flow cytometry experiments.In addition, the Eca-109 and TE-1 cells that were irradiated following IGF-1r knockdown contained 16.2% and 20.3% apoptotic cells, respectively.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Qilu Hospital of Shandong University, Wenhua Western Road 107, Jinan 250012 Shandong Province, China. guxiaomengff@126.com.

ABSTRACT

Background: Esophageal squamous cell carcinoma (ESCC) is a prevalent fatal cancer worldwide, and the number of deaths due to this disease is increasing. Due to ESCC resistance to chemotherapy and radiation treatment, new therapies are urgently needed for the improvement of ESCC patient clinical outcomes.

Methods: Eca-109 and TE-1 cells were transfected with 100 nM IGF-1r siRNA, and a combination of IGF-1r siRNA and radiation therapy was tested in vitro and in vivo. The effects of IGF-1r siRNA were determined through Western blotting and flow cytometry experiments.

Results: After radiotherapy, the number of IGF-1r siRNA-transfected Eca-109 cells decreased by approximately 67.3%, and a 78.9% reduction was observed in the transfected TE-1 cells. In addition, the Eca-109 and TE-1 cells that were irradiated following IGF-1r knockdown contained 16.2% and 20.3% apoptotic cells, respectively.

Conclusions: The results of the current study suggest that IGF-1r knockdown may enhance the radiation sensitivity of ESCC and increase the therapeutic effects of radiation both in vitro and in vivo. These results provide strong evidence that the targeted application of siRNA will enable the development of new therapeutic strategies for the clinical treatment of ESCC patients.

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Therapeutic effect of irradiation combined withIGF-1rsiRNAin vivo. The survival fraction after treatment is shown for (A) Eca-109 and (B) TE-1 cells, respectively. Irradiation alone enhanced tumor growth inhibition and led to shorter survival times than the combination treatment. The tumor volume was calculated at the indicated times in the (C) Eca-109 and (D) TE-1 cell groups, respectively. The statistical significance of the tumor volume changes was calculated using Student’s t-test.
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Fig4: Therapeutic effect of irradiation combined withIGF-1rsiRNAin vivo. The survival fraction after treatment is shown for (A) Eca-109 and (B) TE-1 cells, respectively. Irradiation alone enhanced tumor growth inhibition and led to shorter survival times than the combination treatment. The tumor volume was calculated at the indicated times in the (C) Eca-109 and (D) TE-1 cell groups, respectively. The statistical significance of the tumor volume changes was calculated using Student’s t-test.

Mentions: The therapeutic efficacy of combination treatment was also investigated through in vivo tumor xenograft studies after injecting Eca-109 and TE-1 cells. The tumor volumes and survival rates were evaluated 14 days after cell injection in the different treated groups. The tumor volumes were 3.4 ± 0.2 cm3 in the Eca-109 group and 3.8 ± 0.1 cm3 in the TE-1 group after treatment with phosphate buffered saline (negative control group). After radiotherapy alone, the tumor volume decreased significantly both in the Eca-109 (2.1 ± 0.1 cm3) and TE-1 cells (2.4 ± 0.1 cm3) (P <0.05, n =8). In the group that received IGF-1r siRNA treatment alone, the tumor volume was also reduced (2.8 ± 0.1 cm3 for Eca-109 cells; 3.1 ± 0.1 cm3 for TE-1 cells) (P <0.05, n =8). Notably, it was clear that the tumors were much smaller after irradiation in the presence of IGF-1r siRNA transfection than in any single treatment group (1.1 ± 0.2 cm3 in the Eca-109 group; 0.8 ± 0.1 cm3 in the TE-1 group) (P <0.001, n =8) (Figure 4A). In addition, the survival rates of the tumor-bearing mice were also calculated after different therapeutic strategies. The results showed that the combination therapy significantly enhanced the survival rate compared to the groups with a single treatment (Figure 4B). These in vivo results confirmed that IGF-1r silencing can increase the radiation sensitivity of ESCC tumors in this established tumor model.Figure 4


Silencing of insulin-like growth factor-1 receptor enhances the radiation sensitivity of human esophageal squamous cell carcinoma in vitro and in vivo.

Zhao H, Gu X - World J Surg Oncol (2014)

Therapeutic effect of irradiation combined withIGF-1rsiRNAin vivo. The survival fraction after treatment is shown for (A) Eca-109 and (B) TE-1 cells, respectively. Irradiation alone enhanced tumor growth inhibition and led to shorter survival times than the combination treatment. The tumor volume was calculated at the indicated times in the (C) Eca-109 and (D) TE-1 cell groups, respectively. The statistical significance of the tumor volume changes was calculated using Student’s t-test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4232704&req=5

Fig4: Therapeutic effect of irradiation combined withIGF-1rsiRNAin vivo. The survival fraction after treatment is shown for (A) Eca-109 and (B) TE-1 cells, respectively. Irradiation alone enhanced tumor growth inhibition and led to shorter survival times than the combination treatment. The tumor volume was calculated at the indicated times in the (C) Eca-109 and (D) TE-1 cell groups, respectively. The statistical significance of the tumor volume changes was calculated using Student’s t-test.
Mentions: The therapeutic efficacy of combination treatment was also investigated through in vivo tumor xenograft studies after injecting Eca-109 and TE-1 cells. The tumor volumes and survival rates were evaluated 14 days after cell injection in the different treated groups. The tumor volumes were 3.4 ± 0.2 cm3 in the Eca-109 group and 3.8 ± 0.1 cm3 in the TE-1 group after treatment with phosphate buffered saline (negative control group). After radiotherapy alone, the tumor volume decreased significantly both in the Eca-109 (2.1 ± 0.1 cm3) and TE-1 cells (2.4 ± 0.1 cm3) (P <0.05, n =8). In the group that received IGF-1r siRNA treatment alone, the tumor volume was also reduced (2.8 ± 0.1 cm3 for Eca-109 cells; 3.1 ± 0.1 cm3 for TE-1 cells) (P <0.05, n =8). Notably, it was clear that the tumors were much smaller after irradiation in the presence of IGF-1r siRNA transfection than in any single treatment group (1.1 ± 0.2 cm3 in the Eca-109 group; 0.8 ± 0.1 cm3 in the TE-1 group) (P <0.001, n =8) (Figure 4A). In addition, the survival rates of the tumor-bearing mice were also calculated after different therapeutic strategies. The results showed that the combination therapy significantly enhanced the survival rate compared to the groups with a single treatment (Figure 4B). These in vivo results confirmed that IGF-1r silencing can increase the radiation sensitivity of ESCC tumors in this established tumor model.Figure 4

Bottom Line: Eca-109 and TE-1 cells were transfected with 100 nM IGF-1r siRNA, and a combination of IGF-1r siRNA and radiation therapy was tested in vitro and in vivo.The effects of IGF-1r siRNA were determined through Western blotting and flow cytometry experiments.In addition, the Eca-109 and TE-1 cells that were irradiated following IGF-1r knockdown contained 16.2% and 20.3% apoptotic cells, respectively.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Qilu Hospital of Shandong University, Wenhua Western Road 107, Jinan 250012 Shandong Province, China. guxiaomengff@126.com.

ABSTRACT

Background: Esophageal squamous cell carcinoma (ESCC) is a prevalent fatal cancer worldwide, and the number of deaths due to this disease is increasing. Due to ESCC resistance to chemotherapy and radiation treatment, new therapies are urgently needed for the improvement of ESCC patient clinical outcomes.

Methods: Eca-109 and TE-1 cells were transfected with 100 nM IGF-1r siRNA, and a combination of IGF-1r siRNA and radiation therapy was tested in vitro and in vivo. The effects of IGF-1r siRNA were determined through Western blotting and flow cytometry experiments.

Results: After radiotherapy, the number of IGF-1r siRNA-transfected Eca-109 cells decreased by approximately 67.3%, and a 78.9% reduction was observed in the transfected TE-1 cells. In addition, the Eca-109 and TE-1 cells that were irradiated following IGF-1r knockdown contained 16.2% and 20.3% apoptotic cells, respectively.

Conclusions: The results of the current study suggest that IGF-1r knockdown may enhance the radiation sensitivity of ESCC and increase the therapeutic effects of radiation both in vitro and in vivo. These results provide strong evidence that the targeted application of siRNA will enable the development of new therapeutic strategies for the clinical treatment of ESCC patients.

Show MeSH
Related in: MedlinePlus