Limits...
Experimental study on the regulation of erlotinib-induced radiosensitization with an anti-c-MET monoclonal antibody.

Zhuang HQ, Zhuang H, Bo Q, Guo Y, Wang J, Zhao LJ, Yuan ZY, Wang P - Cancer Cell Int. (2014)

Bottom Line: The expression of c-MET in colony-forming cells in the combined group significantly increased, and the blockade of c-MET activity significantly enhanced the radiosensitizing effect of erlotinib.The expression of c-Met, p-c-MET, PI3K, AKT, and p-AKT among colony-forming cells significantly decreased upon the inhibition of c-MET.The blockade of the c-MET-PI3K-AKT signaling pathway enhanced the radiosensitizing effect of erlotinib.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin, China ; Tianjin Lung Cancer Center, Tianjin, China.

ABSTRACT

Purpose: Erlotinib is a novel therapeutic agent for cancer treatment. This study was performed to investigate the role of c-MET-PI3K-AKT pathway in the regulation of erlotinib-induced radiosensitization.

Methods: A973 lung adenocarcinoma cells treated with 6 Gy of radiation were incubated in the presence of erlotinib. The apoptotic rate after 24 hours, the colony-formating rate after 14 days, and changes in the c-MET expression levels after 14 days of irradiation were examined. Surviving fractions in different treatment groups (blank control, radiation alone, erlotinib alone, anti-c-MET monoclonal antibody alone, combined erlotinib and radiation, and combined erlotinib and radiation with anti-c-MET monoclonal antibody groups) were determined, the survival curves were plotted, and the sensitizer enhancement ratio was calculated using colony formation assays. Expressions of c-MET, p-c-MET, PI3K, AKT, and p-AKT in cells in different treatment groups were examined by Western blot analysis.

Results: The apoptotic rate in the combined erlotinib and radiation group was higher than those in single treatment groups; however, the colony-forming rate remained approximately 2.04 ± 1.02%. The expression of c-MET in colony-forming cells in the combined group significantly increased, and the blockade of c-MET activity significantly enhanced the radiosensitizing effect of erlotinib. The expression of c-Met, p-c-MET, PI3K, AKT, and p-AKT among colony-forming cells significantly decreased upon the inhibition of c-MET.

Conclusions: Upregulated activity of the c-MET-PI3K-AKT pathway was found to be important for cell survival under combined the treatment with erlotinib and radiation. The blockade of the c-MET-PI3K-AKT signaling pathway enhanced the radiosensitizing effect of erlotinib.

No MeSH data available.


Related in: MedlinePlus

The expression of c-MET in colony-forming cells after combined treatment with erlotinib (20 nM) and radiation (6Gy). M1: the cell of c-MET non-expression. M2: the cell of c-MET expression. The expressions of c-MET (M2) were as follows: (A) Control group: 12.25 ± 2.17%. (B) Erlotinib group: 23.36 ± 3.16%. (C) Radiation group: 27.45 ± 3.79%. (D) combined treatment with erlotinib and radiation group: 75.35 ± 6.33%.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4263203&req=5

Fig2: The expression of c-MET in colony-forming cells after combined treatment with erlotinib (20 nM) and radiation (6Gy). M1: the cell of c-MET non-expression. M2: the cell of c-MET expression. The expressions of c-MET (M2) were as follows: (A) Control group: 12.25 ± 2.17%. (B) Erlotinib group: 23.36 ± 3.16%. (C) Radiation group: 27.45 ± 3.79%. (D) combined treatment with erlotinib and radiation group: 75.35 ± 6.33%.

Mentions: Cells from the blank control group, the erlotinib alone group, the radiation (6 Gy) alone group, and the combined erlotinib and radiation group after 14 days of treatment were collected, and the results of the flow cytometry analysis showed that the expression rates of c-MET in these groups were 12.25 ± 2.17%, 23.36 ± 3.16%, 27.45 ± 3.79%, and 75.35 ± 6.33%, respectively. Compared to other groups, the expression rate of c-MET in the combined treatment group significantly increased (Figure 2, ANOVA analysis, P < 0.05). These results showed that both radiation and erlotinib were contributing factors to the increased c-MET expression. Moreover, the combination of radiation and erlotinib had a synergistic effect on the upregulation of c-MET expression.Figure 2


Experimental study on the regulation of erlotinib-induced radiosensitization with an anti-c-MET monoclonal antibody.

Zhuang HQ, Zhuang H, Bo Q, Guo Y, Wang J, Zhao LJ, Yuan ZY, Wang P - Cancer Cell Int. (2014)

The expression of c-MET in colony-forming cells after combined treatment with erlotinib (20 nM) and radiation (6Gy). M1: the cell of c-MET non-expression. M2: the cell of c-MET expression. The expressions of c-MET (M2) were as follows: (A) Control group: 12.25 ± 2.17%. (B) Erlotinib group: 23.36 ± 3.16%. (C) Radiation group: 27.45 ± 3.79%. (D) combined treatment with erlotinib and radiation group: 75.35 ± 6.33%.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4263203&req=5

Fig2: The expression of c-MET in colony-forming cells after combined treatment with erlotinib (20 nM) and radiation (6Gy). M1: the cell of c-MET non-expression. M2: the cell of c-MET expression. The expressions of c-MET (M2) were as follows: (A) Control group: 12.25 ± 2.17%. (B) Erlotinib group: 23.36 ± 3.16%. (C) Radiation group: 27.45 ± 3.79%. (D) combined treatment with erlotinib and radiation group: 75.35 ± 6.33%.
Mentions: Cells from the blank control group, the erlotinib alone group, the radiation (6 Gy) alone group, and the combined erlotinib and radiation group after 14 days of treatment were collected, and the results of the flow cytometry analysis showed that the expression rates of c-MET in these groups were 12.25 ± 2.17%, 23.36 ± 3.16%, 27.45 ± 3.79%, and 75.35 ± 6.33%, respectively. Compared to other groups, the expression rate of c-MET in the combined treatment group significantly increased (Figure 2, ANOVA analysis, P < 0.05). These results showed that both radiation and erlotinib were contributing factors to the increased c-MET expression. Moreover, the combination of radiation and erlotinib had a synergistic effect on the upregulation of c-MET expression.Figure 2

Bottom Line: The expression of c-MET in colony-forming cells in the combined group significantly increased, and the blockade of c-MET activity significantly enhanced the radiosensitizing effect of erlotinib.The expression of c-Met, p-c-MET, PI3K, AKT, and p-AKT among colony-forming cells significantly decreased upon the inhibition of c-MET.The blockade of the c-MET-PI3K-AKT signaling pathway enhanced the radiosensitizing effect of erlotinib.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin, China ; Tianjin Lung Cancer Center, Tianjin, China.

ABSTRACT

Purpose: Erlotinib is a novel therapeutic agent for cancer treatment. This study was performed to investigate the role of c-MET-PI3K-AKT pathway in the regulation of erlotinib-induced radiosensitization.

Methods: A973 lung adenocarcinoma cells treated with 6 Gy of radiation were incubated in the presence of erlotinib. The apoptotic rate after 24 hours, the colony-formating rate after 14 days, and changes in the c-MET expression levels after 14 days of irradiation were examined. Surviving fractions in different treatment groups (blank control, radiation alone, erlotinib alone, anti-c-MET monoclonal antibody alone, combined erlotinib and radiation, and combined erlotinib and radiation with anti-c-MET monoclonal antibody groups) were determined, the survival curves were plotted, and the sensitizer enhancement ratio was calculated using colony formation assays. Expressions of c-MET, p-c-MET, PI3K, AKT, and p-AKT in cells in different treatment groups were examined by Western blot analysis.

Results: The apoptotic rate in the combined erlotinib and radiation group was higher than those in single treatment groups; however, the colony-forming rate remained approximately 2.04 ± 1.02%. The expression of c-MET in colony-forming cells in the combined group significantly increased, and the blockade of c-MET activity significantly enhanced the radiosensitizing effect of erlotinib. The expression of c-Met, p-c-MET, PI3K, AKT, and p-AKT among colony-forming cells significantly decreased upon the inhibition of c-MET.

Conclusions: Upregulated activity of the c-MET-PI3K-AKT pathway was found to be important for cell survival under combined the treatment with erlotinib and radiation. The blockade of the c-MET-PI3K-AKT signaling pathway enhanced the radiosensitizing effect of erlotinib.

No MeSH data available.


Related in: MedlinePlus