Limits...
Significance of c-MET overexpression in cytotoxic anticancer drug-resistant small-cell lung cancer cells.

Ozasa H, Oguri T, Maeno K, Takakuwa O, Kunii E, Yagi Y, Uemura T, Kasai D, Miyazaki M, Niimi A - Cancer Sci. (2014)

Bottom Line: The c-MET receptor tyrosine kinase is the receptor for hepatocyte growth factor.Furthermore, the number of c-MET gene loci was increased in the resistant cells compared to the parental cells.Our results add a new strategy, the targeting of c-MET, for overcoming resistance to cytotoxic agents in small-cell lung cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology and Immunology, Nagoya City University, Nagoya, Japan; Department of Multidisciplinary Cancer Treatment, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Show MeSH

Related in: MedlinePlus

Knockdown of c-MET expression by siRNA in small-cell lung cancer cells. (a) c-MET gene expression was examined using real-time RT-PCR. (b) c-MET and p-MET protein expression was determined using Western blotting. (c) Growth inhibition of stepwise 7-ethyl-10-hydroxycamptothesin (SN-38) or paclitaxel (TXL) concentration in SN-38-resistant (PC-6/SN-38) or TXL-resistant (PC-6/TXL) cells transfected with c-MET siRNA (si MET; ▴) or negative-control (▪) was examined by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) assay.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4317853&req=5

fig03: Knockdown of c-MET expression by siRNA in small-cell lung cancer cells. (a) c-MET gene expression was examined using real-time RT-PCR. (b) c-MET and p-MET protein expression was determined using Western blotting. (c) Growth inhibition of stepwise 7-ethyl-10-hydroxycamptothesin (SN-38) or paclitaxel (TXL) concentration in SN-38-resistant (PC-6/SN-38) or TXL-resistant (PC-6/TXL) cells transfected with c-MET siRNA (si MET; ▴) or negative-control (▪) was examined by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) assay.

Mentions: We knocked down c-MET expression by siRNA against the c-MET gene, to confirm whether c-MET overexpression activated c-MET signaling resulting in resistance to the cytotoxic anticancer drugs. The levels of c-MET gene expression in PC-6/SN-38 or PC-6/TXL cells transfected with siRNA against the c-MET gene were significantly decreased by 30% or 35% relative to the cells with negative-control (Fig. 3a). The levels of c-MET and p-MET protein in PC-6/SN-38 or PC-6/TXL cells with siRNA against the c-MET gene were also downregulated (Fig. 3b). In addition, the growth inhibition of SN-38 in PC-6/SN-38 cells with c-MET siRNA was improved relative to the cells with negative-control (Fig. 3c). We also obtained the same result in PC-6/TXL cells with c-MET siRNA (Fig. 3c).


Significance of c-MET overexpression in cytotoxic anticancer drug-resistant small-cell lung cancer cells.

Ozasa H, Oguri T, Maeno K, Takakuwa O, Kunii E, Yagi Y, Uemura T, Kasai D, Miyazaki M, Niimi A - Cancer Sci. (2014)

Knockdown of c-MET expression by siRNA in small-cell lung cancer cells. (a) c-MET gene expression was examined using real-time RT-PCR. (b) c-MET and p-MET protein expression was determined using Western blotting. (c) Growth inhibition of stepwise 7-ethyl-10-hydroxycamptothesin (SN-38) or paclitaxel (TXL) concentration in SN-38-resistant (PC-6/SN-38) or TXL-resistant (PC-6/TXL) cells transfected with c-MET siRNA (si MET; ▴) or negative-control (▪) was examined by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) assay.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317853&req=5

fig03: Knockdown of c-MET expression by siRNA in small-cell lung cancer cells. (a) c-MET gene expression was examined using real-time RT-PCR. (b) c-MET and p-MET protein expression was determined using Western blotting. (c) Growth inhibition of stepwise 7-ethyl-10-hydroxycamptothesin (SN-38) or paclitaxel (TXL) concentration in SN-38-resistant (PC-6/SN-38) or TXL-resistant (PC-6/TXL) cells transfected with c-MET siRNA (si MET; ▴) or negative-control (▪) was examined by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) assay.
Mentions: We knocked down c-MET expression by siRNA against the c-MET gene, to confirm whether c-MET overexpression activated c-MET signaling resulting in resistance to the cytotoxic anticancer drugs. The levels of c-MET gene expression in PC-6/SN-38 or PC-6/TXL cells transfected with siRNA against the c-MET gene were significantly decreased by 30% or 35% relative to the cells with negative-control (Fig. 3a). The levels of c-MET and p-MET protein in PC-6/SN-38 or PC-6/TXL cells with siRNA against the c-MET gene were also downregulated (Fig. 3b). In addition, the growth inhibition of SN-38 in PC-6/SN-38 cells with c-MET siRNA was improved relative to the cells with negative-control (Fig. 3c). We also obtained the same result in PC-6/TXL cells with c-MET siRNA (Fig. 3c).

Bottom Line: The c-MET receptor tyrosine kinase is the receptor for hepatocyte growth factor.Furthermore, the number of c-MET gene loci was increased in the resistant cells compared to the parental cells.Our results add a new strategy, the targeting of c-MET, for overcoming resistance to cytotoxic agents in small-cell lung cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology and Immunology, Nagoya City University, Nagoya, Japan; Department of Multidisciplinary Cancer Treatment, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Show MeSH
Related in: MedlinePlus