The efficacy of verapamil on the drug efflux pumps of hepatocarcinoma cells

碩士 === 國立中山大學 === 生物醫學研究所 === 97 === Cancer remains the most cause death disease in Taiwan at least ten years. Liver cancer, which consists predominantly of hepatocellular carcinoma (HCC), is the most common cause of cancer mortality in men and the second most in women. Not only liver section and li...

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Main Authors: Tsung-hsien Lee, 李宗憲
Other Authors: Angela Chen
Format: Others
Language:zh-TW
Published: 2009
Online Access:http://ndltd.ncl.edu.tw/handle/7e2n57
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spelling ndltd-TW-097NSYS51140072019-05-15T19:27:45Z http://ndltd.ncl.edu.tw/handle/7e2n57 The efficacy of verapamil on the drug efflux pumps of hepatocarcinoma cells 維拉帕米對於肝癌細胞排藥幫浦功能的影響 Tsung-hsien Lee 李宗憲 碩士 國立中山大學 生物醫學研究所 97 Cancer remains the most cause death disease in Taiwan at least ten years. Liver cancer, which consists predominantly of hepatocellular carcinoma (HCC), is the most common cause of cancer mortality in men and the second most in women. Not only liver section and liver transplantation are used in HCC therapy but also local ablation therapy and transarterial therapy. Transarterial chemoembolization (TACE) is one of the local therapies that inject chemotherapeutic drugs directly into liver tumor. However, drug resistance is the mainly restriction in patient after chemotherapy. Moreover, it is known that drug resistance was associated to over-expression of certain ABC transporter genes, especially ABCB1, ABCG2, and ABCC family in cancer cell and those ABC transporters were also expressed in liver. Base on clinical study, they use 5-fluororuacil, cisplatin and mitomycin-C for liver cancer treatment. In this study, we hypothesized that cancer therapies may be augmented through blocked the drug efflux ABC channels with the ABC transporter inhibitors such as verapamil. The associations among drug treatments, inhibitor incorporation and the expression of ABC transporters were evaluated in HepG2 and Hep3B cells. MTT assay demonstrated that the cell viability was considerable decreased by treating triple drugs with verapamil. RT-PCR data showed that ABC transporters mRNA expression has no significantly change. However, membrane ABCB1 and ABCG2 were induced after drugs and inhibitors treatment either 1 or 24 hours by flow cytometry analysis. P-glycoprotein functional assay also showed p-glycoprotein was inhibited by verapamil, and hence Rhodamine 123 retention was increased. Taken together, there are different response of ABC transporters in HepG2 and Hep3B after drugs and inhibitors treatment. Membrane ABCB1 and ABCG2 were induced by drugs and inhibitors treatment. However, p-glycoprotein’s function was restrained simultaneously by inhibitors treatment. Therefore, verapamil can enhance cell death by inhibiting ABC transporters and its cytotoxic effect rather than the increased expression of ABC transporters. This finding might provide a better way in liver cancer therapy. Angela Chen 陳和瑟 2009 學位論文 ; thesis 146 zh-TW
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description 碩士 === 國立中山大學 === 生物醫學研究所 === 97 === Cancer remains the most cause death disease in Taiwan at least ten years. Liver cancer, which consists predominantly of hepatocellular carcinoma (HCC), is the most common cause of cancer mortality in men and the second most in women. Not only liver section and liver transplantation are used in HCC therapy but also local ablation therapy and transarterial therapy. Transarterial chemoembolization (TACE) is one of the local therapies that inject chemotherapeutic drugs directly into liver tumor. However, drug resistance is the mainly restriction in patient after chemotherapy. Moreover, it is known that drug resistance was associated to over-expression of certain ABC transporter genes, especially ABCB1, ABCG2, and ABCC family in cancer cell and those ABC transporters were also expressed in liver. Base on clinical study, they use 5-fluororuacil, cisplatin and mitomycin-C for liver cancer treatment. In this study, we hypothesized that cancer therapies may be augmented through blocked the drug efflux ABC channels with the ABC transporter inhibitors such as verapamil. The associations among drug treatments, inhibitor incorporation and the expression of ABC transporters were evaluated in HepG2 and Hep3B cells. MTT assay demonstrated that the cell viability was considerable decreased by treating triple drugs with verapamil. RT-PCR data showed that ABC transporters mRNA expression has no significantly change. However, membrane ABCB1 and ABCG2 were induced after drugs and inhibitors treatment either 1 or 24 hours by flow cytometry analysis. P-glycoprotein functional assay also showed p-glycoprotein was inhibited by verapamil, and hence Rhodamine 123 retention was increased. Taken together, there are different response of ABC transporters in HepG2 and Hep3B after drugs and inhibitors treatment. Membrane ABCB1 and ABCG2 were induced by drugs and inhibitors treatment. However, p-glycoprotein’s function was restrained simultaneously by inhibitors treatment. Therefore, verapamil can enhance cell death by inhibiting ABC transporters and its cytotoxic effect rather than the increased expression of ABC transporters. This finding might provide a better way in liver cancer therapy.
author2 Angela Chen
author_facet Angela Chen
Tsung-hsien Lee
李宗憲
author Tsung-hsien Lee
李宗憲
spellingShingle Tsung-hsien Lee
李宗憲
The efficacy of verapamil on the drug efflux pumps of hepatocarcinoma cells
author_sort Tsung-hsien Lee
title The efficacy of verapamil on the drug efflux pumps of hepatocarcinoma cells
title_short The efficacy of verapamil on the drug efflux pumps of hepatocarcinoma cells
title_full The efficacy of verapamil on the drug efflux pumps of hepatocarcinoma cells
title_fullStr The efficacy of verapamil on the drug efflux pumps of hepatocarcinoma cells
title_full_unstemmed The efficacy of verapamil on the drug efflux pumps of hepatocarcinoma cells
title_sort efficacy of verapamil on the drug efflux pumps of hepatocarcinoma cells
publishDate 2009
url http://ndltd.ncl.edu.tw/handle/7e2n57
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