| Summary: | 碩士 === 臺灣大學 === 生理學研究所 === 98 === Lung cancer is one of the tenth leading causes of death in Taiwan. The
average survival duration for patients with lung cancer is about 9-12 months
and overall 5-year survival rate is about 10%. There are less than 20% lung
cancer patients able to undergo curative resection. 80% of lung cancer patients
undergo surgery died of metastasis within two years. More effective treatments
for this devastating disease are urgently needed. Based on our previous findings,
IAA induced cytochrome C release resulting in activation of caspase-3 and
nuclear condensation in non-small cell lung cancer (NSCLC). In this study, we
investigate possible molecular mechanism(s) of how IAA induced cell death in
human lung cancer cell lines. Our results showed that IAA induced
dose-dependent cell death as well as inhibited migration in anchorage
dependent and anchorage independent assays. These responses could be
reversed by dithiothreitol (DTT) or N-acetyl-L cystein (NAC) in most tested
lung cancer cell lines, such as A549, H1299, H522, HOP62, H23, EKVX,
PC14, H1975, H441 and H460. Though RT-PCR and microarray analysis,
Notch-3 can be confirmed as the target of IAA. Pbx-1 is predicted as
downstream oncogene of Notch-3. Cells treated with IAA for 16 or 24 hours,
RT-PCR assay showed Pbx-1 mRNA suppression. However, this symptom can
be reversed by DTT or NAC. As a conclusion, Notch-3 and it’s downstream,
Pbx-1, involved in IAA-induced cell death, which suggesting that inactivation
of Notch-3 or Pbx-1 may be a potential therapy for lung cancer.
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