| Summary: | 博士 === 國立中山大學 === 生物醫學研究所 === 106 === 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.
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