Browsing by Author "Lee, Nien-Hung"

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Apicidin-resistant HA22T hepatocellular carcinoma cells massively promote pro-survival capability via IGF-IR/PI3K/Akt signaling pathway activation
(2014-01-01)
Hsu, Hsi-Hsien
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Cheng, Li-Hao
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Ho, Tsung-Jung
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Kuo, Wei-Wen
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Lin, Yueh-Min
Despite rapid advances in the diagnostic and surgical procedures, hepatocellular carcinoma (HCC) remains one of the most difficult human malignancies to treat. This may be due to the chemoresistant behaviors of HCC. It is believed that acquired resistance could be overcome and improve the overall survival of HCC patients by understanding the mechanisms of chemoresistance in HCC. A stable HA22T cancer line, which is chronically resistant to a histone deacetylase inhibitor, was established. After comparing the molecular mechanism of apicidin-R HA22T cells to parental ones by Western blotting, cell cycle-regulated proteins did not change in apicidin-R cells, but apicidin-R cells were more proliferative and had higher tumor growth (wound-healing assay and nude mice xenograft model). Moreover, apicidin-R cells displayed increased levels of p-IGF-IR, p-PI3K, p-Akt, Bcl-xL, and Bcl-2 but also significantly inhibited the tumor suppressor PTEN protein and apoptotic pathways when compared to the parental strain. Therefore, the highly proliferative effect of apicidin-R HA22T cells was blocked by Akt knockdown. For all these findings, we believe that novel strategies to attenuate IGF-IR/PI3K/Akt signaling could overcome chemoresistance toward the improvement of overall survival of HCC patients.
Dung-shen (Codonopsis pilosula) attenuated the cardiac-impaired insulin-like growth factor II receptor pathway on myocardial cells
(2013-05-15)
Tsai, Kun-Hsi
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Lee, Nien-Hung
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Chen, Guei-Ying
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Hu, Wei-Syun
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Tsai, Chen-Yen
Previous studies from our lab showed that increase in AngIl in H9c2 cells causes elevated IGFII and IGFIIR through MEK and JNK, leading to rise in intracellular calcium, calcineurin activation by PLC-beta 3 via G alpha q, insertion into mitochondrial membranes of Bad, and apoptosis via caspases 9 and 3. Codonopsis pilosula is traditionally used to lower blood pressure. The purpose of our study is to investigate if C. pilosula attenuates AngII plus Leu(27)-IGFII-induced calcium influx and apoptosis in H9c2 cardiomyoblasts. C pilosula significantly attenuated AngII induced IGFIIR promoter activity. Leu(27)-IGFII was applied to enhance the Angll effect. C pilosula also reversed Ca2+ influx, MOMP and apoptosis increased by AngIl plus Leu(27)-IGFIL Molecular markers in IGFIIR apoptotic pathway (IGFIIR, calcineurin, etc.) and IGFIIR-G alpha q association were downregulated by C pilosula. However, p-Bad(Ser136) and BcI-2 were increased. Therefore, C pilosula suppresses Angll plus Leu(27)-IGFII-induced IGFII/IGFIIR pathway in myocardial cells. (C) 2012 Elsevier Ltd. All rights reserved.
Dung-Shen Downregulates the Synergistic Apoptotic Effects of Angiotensin II Plus Leu 27-IGF II on Cardiomyoblasts
(2014-01-01)
Chang, Ko-Shih
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Lee, Nien-Hung
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Kuo, Wei-Wen
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Hu, Wei-Syun
;
Chang, Mu-Hsin
Background: Insulin growth factor II (IGFII) is expressed after ischemic stress in pig hearts and after myocardial infarction in humans. However, its receptor (IGFIIR) cannot be found in normal adult hearts. Moreover, a mouse IGFII overexpression model showed a heart and kidney hypertrophy phenomenon similar to Beckwith-Wiedemann syndrome in humans. The previous studies from our lab showed that an increase in AngII in H9c2 cells causes an elevation in IGFII and IGFIIR through MEK and JNK activation, leading to a rise in intracellular Ca2+ ions, activation of calcineurin by PLC-beta 3 via Gaq, insertion into mitochondrial membranes of BAD, and apoptosis via activation of caspases 9 and 3. Codonopsis pilosula (Dung-shen) has various uses in traditional Chinese medicine, including lowering blood pressure, and increasing red and white blood cell counts. Methods: The purpose of our study is to investigate whether the addition of C. pilosula will attenuate the Angl I plus Leu27-IGF11-induced apoptosis in H9c2 cardiomyoblast cells. Results: From MTT [3-(4, 5-dimethy1-2-thiazolyI)-2, 5-dipheny1-2-tetrazolium bromide] results, it was revealed that Angll plus Leu27-IGFII significantly reduced cell viability, which was reversed by C. pilosula. Additionally, C. pilosula also reversed apoptosis (TUNEL staining) increased by Angll plus Leu27-IGFII. Up-regulation of caspase 3 by Angl I plus Leu27-IGFII was attenuated by C. pilosula treatment, as shown in western blotting assay and immunofluorescence microscopy results. Conclusions: C. pilosula is able to suppress the apoptotic pathway enhanced by Angl I plus Leu27-IGFII in myocardial cells.