Title page for etd-0712118-213436


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URN etd-0712118-213436
Author Han-Lin Chou
Author's Email Address d992050005@gmail.com
Statistics This thesis had been viewed 5565 times. Download 0 times.
Department Institute of Biomedical Sciences
Year 2017
Semester 2
Degree Ph.D.
Type of Document
Language zh-TW.Big5 Chinese
Title Induction of oxidative stress and apoptosis in human non-small cell lung cancer cells by camptothecin combined with quinone- or acetamide-containing compound
Date of Defense 2018-07-25
Page Count 142
Keyword
  • quinone-containing compound
  • acetamide-containing compound
  • apoptosis
  • human non-small cell lung cancer cells
  • oxidative stress
  • camptothecin
  • Abstract Lung cancer is one of the highly lethal cancers among all cancer types.
    Non-small cell lung cancer (NSCLC) is the most common types in lung cancer,
    accounting for 85%. Chemotherapy is currently the main treatment for patients with
    NSCLC.  However,  clinical  statistics  found  that  the  treatment  of  a  single
    chemotherapy drug is not effective for lung cancer patients. Drug resistance is one of
    the reasons for the poor efficacy of chemotherapeutic agents for lung cancer. In order
    to increase the effectiveness of anti-cancer therapy, the combination of two or more
    chemotherapeutic agents is currently the main treatment for NSCLC. The strategy of
    this treatment is mainly to enhance the effectiveness of drugs in inhibiting cancer cells
    growth. The main direction of this document is the treatment of NSCLC cells with the
    combination of chemotherapeutic agents, and evaluate the effect and mechanism of
    inhibiting cell growth in NSCLC cells. This report is divided into two parts, the first
    part of the thesis is to investigate the effect of quinone compounds on cell apoptosis
    induced by camptothecin (CPT) in non-small cell lung cancer. In this section, we used
    a combination of 4-[2, 3, 5, 6-tetrafluoro-4-(4-hydroxyphenoxy) phenoxy] phenol
    (abbreviated as TFPP) and CPT to treat NSCLC cells. The study found that the
    combination of CPT and TFPP to inhibit the growth of NSCLC through inducing
    apoptosis. In addition, I have found that TFPP can enhance CPT-induced oxidative
    stress, and inhibit the activity of ERK/MAPK (mitogen-activated protein kinases) to
    increase the induction of apoptosis in NSCLC cells. In view of this, drug combination
    may still cause side effects or toxicity to patients. Low-toxic sensitizer has been
    widely evaluated and applied to treat various cancer patients, including lung cancer.
    Therefore, the second part of the thesis is mainly to explore the effect of acetamide
    derivative on CPT-induced apoptosis in NSCLC cells. This part of the use of a combined agent is different from the previous one. I used an acetamide derivative
    N-[2-(morpholin-4-yl) phenyl]-2-{8-oxatricyclo [7.4. 0. 0, 2, 7] trideca-1 (9), 2 (7), 3,
    5, 10, 12-hexaen-4-yloxy} acetamide (abbreviated as NPOA). Although it does not
    have the ability to kill cancer cells by NPOA, we have found that it can sensitize
    NSCLC cells to CPT treatment. Our results showed that NPOA can significantly
    increase CPT-induced apoptosis and inhibit cellular growth in NSCLC cells. In
    addition, we found that NPOA can enhance CPT-induced oxidative stress, and
    activates  the activity  of  JNK/MAPK,  and  increase  the  loss  of  mitochondrial
    membrane potential to induce apoptosis. Both of these parts are based on CPT-based
    treatment, and then combined with other different types of agents as a strategy for
    cancer treatment. Therefore, in the future, it can provide a platform for screening
    CPT-derived drugs (such as irinotecan or topotecan). In addition, the experimental
    spindle is to increase the active oxide in cancer cells as a regulator of cell apoptosis,
    which can provide the future direction in the treatment of cancer patients. Although
    two different compounds can both be combined with CPT and induce apoptosis, it is
    different for regulating intracellular pathways.
    Advisory Committee
  • Cheng Kuang-hung - chair
  • Chang Hsueh-wei - co-chair
  • Wang Hui-min - co-chair
  • Chiu Chien-chih - advisor
  • Huang Hung-wen - advisor
  • Files
  • etd-0712118-213436.pdf
  • Indicate in-campus at 5 year and off-campus access at 5 year.
    Date of Submission 2018-08-13

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