Synergistic antitumor effect of c-Met-dependent oncolytic adenovirus combined with rapamycin in non-small cell lung cancer

碩士 === 國立成功大學 === 微生物及免疫學研究所 === 96 === Lung cancer is a deadly disease with high mortality and morbidity. Approximately 85% of these cases are non-small cell lung cancer (NSCLC) with the rest being small cell lung cancer (SCLC). Like normal cells, lung cancer cells express receptor tyrosine kinases...

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Main Authors: Jeng-Liang Tsai, 蔡政良
Other Authors: Al-Li Shiau
Format: Others
Language:zh-TW
Published: 2008
Online Access:http://ndltd.ncl.edu.tw/handle/09451060211457183819
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spelling ndltd-TW-096NCKU03800112017-06-17T04:31:20Z http://ndltd.ncl.edu.tw/handle/09451060211457183819 Synergistic antitumor effect of c-Met-dependent oncolytic adenovirus combined with rapamycin in non-small cell lung cancer 合併c-Met驅動子調控的溶瘤腺病毒與rapamycin協同抑制非小細胞肺癌 Jeng-Liang Tsai 蔡政良 碩士 國立成功大學 微生物及免疫學研究所 96 Lung cancer is a deadly disease with high mortality and morbidity. Approximately 85% of these cases are non-small cell lung cancer (NSCLC) with the rest being small cell lung cancer (SCLC). Like normal cells, lung cancer cells express receptor tyrosine kinases. The difference is that these receptors may be overexpressed or mutated leading to increased activation. c-Met is a receptor tyrosine kinase whose activation by hepatocyte growth factor can lead to transformation and tumorigenicity. It is also implicated in growth, invasion, and metastasis of various tumors, including lung cancer. Here, we used an E1B 55KD-deleted replication-selective oncolytic adenovirus (Ad.What) driven by the c-Met promoter for the treatment of lung cancer. Ad.What replicated and hence lysed lung cancer cells with c-Met overexpression, whereas it did not induce noticeable cytopathic effects in normal cells. Previous studies showed that combination of oncolytic adenovirus with chemotherapeutic drugs could augment the antitumor efficacy. Rapamycin, a highly selective inhibitor of mammalian target of rapamycin (mTOR) serine/threonine kinase, has shown promise in clinical studies for treating different types of cancer. Accordingly, we combined rapamycin with Ad.What and found that they synergized in inducing cytopathic effects in lung cancer cells. Rapamycin enhanced coxsackievirus and adenovirus receptor (CAR) and αV integrin expression on cancer cells. Ad.What reduced total p70S6K and phosphorylated p70S6K, the downstream effector of mTOR, and induced autophagy. We concluded that the combination of c-Met promoter-driven oncolytic adenovirus with rapamycin has the potential to be an effective strategy for lung cancer treatment. Al-Li Shiau 蕭璦莉 2008 學位論文 ; thesis 49 zh-TW
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description 碩士 === 國立成功大學 === 微生物及免疫學研究所 === 96 === Lung cancer is a deadly disease with high mortality and morbidity. Approximately 85% of these cases are non-small cell lung cancer (NSCLC) with the rest being small cell lung cancer (SCLC). Like normal cells, lung cancer cells express receptor tyrosine kinases. The difference is that these receptors may be overexpressed or mutated leading to increased activation. c-Met is a receptor tyrosine kinase whose activation by hepatocyte growth factor can lead to transformation and tumorigenicity. It is also implicated in growth, invasion, and metastasis of various tumors, including lung cancer. Here, we used an E1B 55KD-deleted replication-selective oncolytic adenovirus (Ad.What) driven by the c-Met promoter for the treatment of lung cancer. Ad.What replicated and hence lysed lung cancer cells with c-Met overexpression, whereas it did not induce noticeable cytopathic effects in normal cells. Previous studies showed that combination of oncolytic adenovirus with chemotherapeutic drugs could augment the antitumor efficacy. Rapamycin, a highly selective inhibitor of mammalian target of rapamycin (mTOR) serine/threonine kinase, has shown promise in clinical studies for treating different types of cancer. Accordingly, we combined rapamycin with Ad.What and found that they synergized in inducing cytopathic effects in lung cancer cells. Rapamycin enhanced coxsackievirus and adenovirus receptor (CAR) and αV integrin expression on cancer cells. Ad.What reduced total p70S6K and phosphorylated p70S6K, the downstream effector of mTOR, and induced autophagy. We concluded that the combination of c-Met promoter-driven oncolytic adenovirus with rapamycin has the potential to be an effective strategy for lung cancer treatment.
author2 Al-Li Shiau
author_facet Al-Li Shiau
Jeng-Liang Tsai
蔡政良
author Jeng-Liang Tsai
蔡政良
spellingShingle Jeng-Liang Tsai
蔡政良
Synergistic antitumor effect of c-Met-dependent oncolytic adenovirus combined with rapamycin in non-small cell lung cancer
author_sort Jeng-Liang Tsai
title Synergistic antitumor effect of c-Met-dependent oncolytic adenovirus combined with rapamycin in non-small cell lung cancer
title_short Synergistic antitumor effect of c-Met-dependent oncolytic adenovirus combined with rapamycin in non-small cell lung cancer
title_full Synergistic antitumor effect of c-Met-dependent oncolytic adenovirus combined with rapamycin in non-small cell lung cancer
title_fullStr Synergistic antitumor effect of c-Met-dependent oncolytic adenovirus combined with rapamycin in non-small cell lung cancer
title_full_unstemmed Synergistic antitumor effect of c-Met-dependent oncolytic adenovirus combined with rapamycin in non-small cell lung cancer
title_sort synergistic antitumor effect of c-met-dependent oncolytic adenovirus combined with rapamycin in non-small cell lung cancer
publishDate 2008
url http://ndltd.ncl.edu.tw/handle/09451060211457183819
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