Study of the Mechanism of Nitric Oxide Reducing Silymarin-induced Growth Inhibition in HepG2 Human Hepatoma Cells
碩士 === 國立陽明大學 === 藥理學研究所 === 97 === Hepatocellular carcinoma (HCC) is one of the most common cancers around the world. Although there are many studies on HCC, effective treatments for HCC are limited. Silymarin is a herbal drug used for the prevention and treatment of liver disease. Previous studies...
Main Authors: | , |
---|---|
Other Authors: | |
Format: | Others |
Language: | zh-TW |
Published: |
2009
|
Online Access: | http://ndltd.ncl.edu.tw/handle/t966tb |
id |
ndltd-TW-097YM005550002 |
---|---|
record_format |
oai_dc |
spelling |
ndltd-TW-097YM0055500022019-05-15T20:07:01Z http://ndltd.ncl.edu.tw/handle/t966tb Study of the Mechanism of Nitric Oxide Reducing Silymarin-induced Growth Inhibition in HepG2 Human Hepatoma Cells 探討一氧化氮減少水飛薊素抑制人類肝癌細胞株HepG2生長之機制探討 Chih-Wei Chen 陳稚唯 碩士 國立陽明大學 藥理學研究所 97 Hepatocellular carcinoma (HCC) is one of the most common cancers around the world. Although there are many studies on HCC, effective treatments for HCC are limited. Silymarin is a herbal drug used for the prevention and treatment of liver disease. Previous studies found that silibinin, the major component of silymarin, showed anti-HCC effects and decreased nitric oxide (NO) production in HepG2 cells. Recently, we have demonstrated cytoprotective functions of NO in hepatoma cells. Firstly, the growth inhibitory effects of silymarin and silibinin on human hepatoma cells were compared. The results showed that silymarin-induced growth inhibition of HepG2 cells was dose- and time-dependent, and silibinin treatment resulted in similar response in HepG2 cells. Furthermore, high dose (100, 200 μg/ml) silymarin treatment resulted in round up and fragmented cell morphology in HepG2 cells. Flowcytometry was used to analyze the cell cycle, and the results showed that silymarin treatment slightly increased the percentage of G2/M phase and apoptotic cells at 72 hr. This study further investigated the cytoprotective effect of NO in silymarin-induced growth inhibition of HepG2 cells. Treatment of HepG2 cells with sodium nitroprusside (SNP), a NO donor, increased the NO level dose dependently. Treatment of HepG2 cells with 0.1 mM to 0.5 mM of SNP significantly inhibited the high dose (100~200 μg/ml) silymarin-induced cell growth inhibition. Moreover, it was found that the NO scavenger, PTIO, blocked the cytoprotective effect of SNP in HepG2 cells and this correlated with a decrease of the SNP-induced intracellular NO level. Western blot analysis revealed the mechanism of silymarin-induced growth inhibition, invoved PI3K/ Akt, MAPK and apoptotic pathway. SNP treatment increased the activity and levels of Akt, ERK and IKK�� protein. These results suggested that the effect of NO on modulation of silymarin-induced growth inhibition effect on HepG2 cells may through PI3K/Akt or MAPK pathways. These results together suggest that nitric oxide may partially reverse the inhibtiory effect of silymarin on hepatoma cells. Chin-Wen Chi Hsin-Chen Lee 戚謹文 李新城 2009 學位論文 ; thesis 88 zh-TW |
collection |
NDLTD |
language |
zh-TW |
format |
Others
|
sources |
NDLTD |
description |
碩士 === 國立陽明大學 === 藥理學研究所 === 97 === Hepatocellular carcinoma (HCC) is one of the most common cancers around the world. Although there are many studies on HCC, effective treatments for HCC are limited. Silymarin is a herbal drug used for the prevention and treatment of liver disease. Previous studies found that silibinin, the major component of silymarin, showed anti-HCC effects and decreased nitric oxide (NO) production in HepG2 cells. Recently, we have demonstrated cytoprotective functions of NO in hepatoma cells. Firstly, the growth inhibitory effects of silymarin and silibinin on human hepatoma cells were compared. The results showed that silymarin-induced growth inhibition of HepG2 cells was dose- and time-dependent, and silibinin treatment resulted in similar response in HepG2 cells. Furthermore, high dose (100, 200 μg/ml) silymarin treatment resulted in round up and fragmented cell morphology in HepG2 cells. Flowcytometry was used to analyze the cell cycle, and the results showed that silymarin treatment slightly increased the percentage of G2/M phase and apoptotic cells at 72 hr. This study further investigated the cytoprotective effect of NO in silymarin-induced growth inhibition of HepG2 cells. Treatment of HepG2 cells with sodium nitroprusside (SNP), a NO donor, increased the NO level dose dependently. Treatment of HepG2 cells with 0.1 mM to 0.5 mM of SNP significantly inhibited the high dose (100~200 μg/ml) silymarin-induced cell growth inhibition. Moreover, it was found that the NO scavenger, PTIO, blocked the cytoprotective effect of SNP in HepG2 cells and this correlated with a decrease of the SNP-induced intracellular NO level. Western blot analysis revealed the mechanism of silymarin-induced growth inhibition, invoved PI3K/ Akt, MAPK and apoptotic pathway. SNP treatment increased the activity and levels of Akt, ERK and IKK�� protein. These results suggested that the effect of NO on modulation of silymarin-induced growth inhibition effect on HepG2 cells may through PI3K/Akt or MAPK pathways. These results together suggest that nitric oxide may partially reverse the inhibtiory effect of silymarin on hepatoma cells.
|
author2 |
Chin-Wen Chi |
author_facet |
Chin-Wen Chi Chih-Wei Chen 陳稚唯 |
author |
Chih-Wei Chen 陳稚唯 |
spellingShingle |
Chih-Wei Chen 陳稚唯 Study of the Mechanism of Nitric Oxide Reducing Silymarin-induced Growth Inhibition in HepG2 Human Hepatoma Cells |
author_sort |
Chih-Wei Chen |
title |
Study of the Mechanism of Nitric Oxide Reducing Silymarin-induced Growth Inhibition in HepG2 Human Hepatoma Cells |
title_short |
Study of the Mechanism of Nitric Oxide Reducing Silymarin-induced Growth Inhibition in HepG2 Human Hepatoma Cells |
title_full |
Study of the Mechanism of Nitric Oxide Reducing Silymarin-induced Growth Inhibition in HepG2 Human Hepatoma Cells |
title_fullStr |
Study of the Mechanism of Nitric Oxide Reducing Silymarin-induced Growth Inhibition in HepG2 Human Hepatoma Cells |
title_full_unstemmed |
Study of the Mechanism of Nitric Oxide Reducing Silymarin-induced Growth Inhibition in HepG2 Human Hepatoma Cells |
title_sort |
study of the mechanism of nitric oxide reducing silymarin-induced growth inhibition in hepg2 human hepatoma cells |
publishDate |
2009 |
url |
http://ndltd.ncl.edu.tw/handle/t966tb |
work_keys_str_mv |
AT chihweichen studyofthemechanismofnitricoxidereducingsilymarininducedgrowthinhibitioninhepg2humanhepatomacells AT chénzhìwéi studyofthemechanismofnitricoxidereducingsilymarininducedgrowthinhibitioninhepg2humanhepatomacells AT chihweichen tàntǎoyīyǎnghuàdànjiǎnshǎoshuǐfēijìsùyìzhìrénlèigānáixìbāozhūhepg2shēngzhǎngzhījīzhìtàntǎo AT chénzhìwéi tàntǎoyīyǎnghuàdànjiǎnshǎoshuǐfēijìsùyìzhìrénlèigānáixìbāozhūhepg2shēngzhǎngzhījīzhìtàntǎo |
_version_ |
1719097310510579712 |