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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2016.1
- 수록면
- 1,312 - 1,323 (12page)
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Purpose: The aim of our study was to explore the relationships between the M2 isoform of pyruvate kinase (PKM2) and the sensitivityof human non-small cell lung cancer (NSCLC) cells to docetaxel in vitro.
Materials and Methods: With the method of plasmid transfection, we silenced the expression of PKM2 successfully in A549 and H460 cells. Western blotting and real-time PCR were applied to detect PKM2 expression at protein and gene levels. Cell viability was examined by CCK8 assay. Cell cycle distribution and apoptosis were examined by flow cytometry. P21 and Bax were detected.
Results: Expression of PKM2 mRNA and protein were significantly decreased by shRNA targeting PKM2. Silencing of PKM2 increaseddocetaxel sensitivity of human NSCLC A549 and H460 cells in a collaborative manner, resulting in strong suppression of cell viability. The results of flow cytometric assays suggested that knockdown of PKM2 or docetaxel treatment, whether used singlyor in combination, blocked the cells in the G2/M phase, which is in consistent with the effect of the two on the expression of p21. Cells with PKM2 silencing were more likely to be induced into apoptosis by docetaxel although knockdown of PKM2 alone can’t induce apoptosis significantly, which is in consistent with the effect of the two on Bax expression.
Conclusion: The results suggest that PKM2 knockdown could serve as a chemosensitizer to docetaxel in non-small lung cancer cells through targeting PKM2, leading to inhibition of cell viability, increase of cell arrest of G2/M phase and apoptosis.
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참고문헌 (38)
참고문헌 신청
Warburg O / 1956 / On the origin of cancer cells / Science 123:309~314
Mazurek S / 2011 / Pyruvate kinase type M2: a key regulator of the metabolic budget system in tumor cells / Int J Biochem Cell Biol 43:969~980
Yeh CS / 2008 / Significance of the glycolytic pathway and glycolysis related-genes in tumorigenesis of human colorectal cancers / Oncol Rep 19:81~91
Gumin´ska M / 1997 / Tumor-specific pyruvate kinase isoenzyme M2 involved in biochemical strategy of energy generation in neoplastic cells / Acta Biochim Pol 44:711~724
Hacker HJ / 1998 / Pyruvate kinase isoenzyme shift from L-type to M2-type is a late event in hepatocarcinogenesis induced in rats by a choline-deficient/DL-ethionine-supplemented diet / Carcinogenesis 19:99~107
Mazurek S / 2011 / Pyruvate kinase type M2: a key regulator of the metabolic budget system in tumor cells / Int J Biochem Cell Biol 43:969~980
Yeh CS / 2008 / Significance of the glycolytic pathway and glycolysis related-genes in tumorigenesis of human colorectal cancers / Oncol Rep 19:81~91
Gumin´ska M / 1997 / Tumor-specific pyruvate kinase isoenzyme M2 involved in biochemical strategy of energy generation in neoplastic cells / Acta Biochim Pol 44:711~724
Hacker HJ / 1998 / Pyruvate kinase isoenzyme shift from L-type to M2-type is a late event in hepatocarcinogenesis induced in rats by a choline-deficient/DL-ethionine-supplemented diet / Carcinogenesis 19:99~107
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