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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.

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Hepatocyte growth factor (HGF) protein expression in cytotoxic anticancer drug-resistant small-cell lung cancer cells, including PC-6 and NCI-H69 parental cells and those resistant to 7-ethyl-10-hydroxycamptothesin (PC-6/SN-38), paclitaxel (PC-6/TXL and H69/TXL), and cisplatin (PC-6/CDDP). (a) Levels of HGF protein expression in cytotoxic anticancer drug-resistant cells were examined by Western blotting. (b) Secretion of HGF in resistant cells was quantified by quantitative ELISA and compared to that in parental cells. (c) Growth inhibition of SN-38 to PC-6 cultured with or without HGF (50 ng/mL) for 2 weeks was examined with the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) assay. *P < 0.05; **P < 0.01.
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fig06: Hepatocyte growth factor (HGF) protein expression in cytotoxic anticancer drug-resistant small-cell lung cancer cells, including PC-6 and NCI-H69 parental cells and those resistant to 7-ethyl-10-hydroxycamptothesin (PC-6/SN-38), paclitaxel (PC-6/TXL and H69/TXL), and cisplatin (PC-6/CDDP). (a) Levels of HGF protein expression in cytotoxic anticancer drug-resistant cells were examined by Western blotting. (b) Secretion of HGF in resistant cells was quantified by quantitative ELISA and compared to that in parental cells. (c) Growth inhibition of SN-38 to PC-6 cultured with or without HGF (50 ng/mL) for 2 weeks was examined with the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) assay. *P < 0.05; **P < 0.01.

Mentions: Hepatocyte growth factor-mediated MET activation was a novel mechanism of the acquired resistance to gefitinib in lung adenocarcinoma.(19,31) Furthermore, HGF has been shown to accelerate the emergence of c-MET amplification in gefitinib-resistant lung cancer cells.(31) In this study, we examined the levels of endogenous HGF expression in PC-6/SN-38, PC-6/TXL, PC-6/CDDP, and NCI-H69/TXL cells by WB. Hepatocyte growth factor protein expression in the resistant cells was upregulated compared with the parental cells (Fig. 6a). The concentration of HGF in cell culture supernatants was significantly higher from PC-6/SN-38, PC-6/TXL, and PC-6/CDDP cells than from PC-6 cells (Fig. 6b). We examined the sensitivity of PC-6 cells to SN-38 after cultured with HGF for 2 weeks. PC-6 cells with HGF were significantly resistant to SN-38 relative to PC-6 cells without HGF (Fig. 6c).


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)

Hepatocyte growth factor (HGF) protein expression in cytotoxic anticancer drug-resistant small-cell lung cancer cells, including PC-6 and NCI-H69 parental cells and those resistant to 7-ethyl-10-hydroxycamptothesin (PC-6/SN-38), paclitaxel (PC-6/TXL and H69/TXL), and cisplatin (PC-6/CDDP). (a) Levels of HGF protein expression in cytotoxic anticancer drug-resistant cells were examined by Western blotting. (b) Secretion of HGF in resistant cells was quantified by quantitative ELISA and compared to that in parental cells. (c) Growth inhibition of SN-38 to PC-6 cultured with or without HGF (50 ng/mL) for 2 weeks was examined with the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) assay. *P < 0.05; **P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4317853&req=5

fig06: Hepatocyte growth factor (HGF) protein expression in cytotoxic anticancer drug-resistant small-cell lung cancer cells, including PC-6 and NCI-H69 parental cells and those resistant to 7-ethyl-10-hydroxycamptothesin (PC-6/SN-38), paclitaxel (PC-6/TXL and H69/TXL), and cisplatin (PC-6/CDDP). (a) Levels of HGF protein expression in cytotoxic anticancer drug-resistant cells were examined by Western blotting. (b) Secretion of HGF in resistant cells was quantified by quantitative ELISA and compared to that in parental cells. (c) Growth inhibition of SN-38 to PC-6 cultured with or without HGF (50 ng/mL) for 2 weeks was examined with the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) assay. *P < 0.05; **P < 0.01.
Mentions: Hepatocyte growth factor-mediated MET activation was a novel mechanism of the acquired resistance to gefitinib in lung adenocarcinoma.(19,31) Furthermore, HGF has been shown to accelerate the emergence of c-MET amplification in gefitinib-resistant lung cancer cells.(31) In this study, we examined the levels of endogenous HGF expression in PC-6/SN-38, PC-6/TXL, PC-6/CDDP, and NCI-H69/TXL cells by WB. Hepatocyte growth factor protein expression in the resistant cells was upregulated compared with the parental cells (Fig. 6a). The concentration of HGF in cell culture supernatants was significantly higher from PC-6/SN-38, PC-6/TXL, and PC-6/CDDP cells than from PC-6 cells (Fig. 6b). We examined the sensitivity of PC-6 cells to SN-38 after cultured with HGF for 2 weeks. PC-6 cells with HGF were significantly resistant to SN-38 relative to PC-6 cells without HGF (Fig. 6c).

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