碩士 / 輔英科技大學 / 醫學檢驗生物技術系碩士班 / 107 / Background/Aims: Lung cancer is one of the leading causes of global deaths. Though lung cancer often used chemotherapy in clinical, it still has extremely serious toxicity and side effects on the body. Fucoidan is a polysaccharide extracted from Fucus vesiculosus that has a wide range of pharmacological properties. The purpose of our present study was to investigate fucoidan enhance low concentration doxorubicin to inhibit chemodrug doxorubicin resistance of human lung adenocarcinoma cell (A549) proliferation and mechanism, we hope to reduce the toxicity and side effects of chemotherapeutic drugs on the human body and achieve the efficacy of natural extracts in adjuvant chemotherapy.
Methods: Long-term stimulation of non-small cell lung cancer cell lines by chemotherapy drugs doxorubicin, to establish a cell line resistant to doxorubicin, and then the natural extract fucoidan is co-treated with drug-resistant cell lines. It was confirmed by MTT assay whether fucoidan enhanced the sensitivity of doxorubicin to drug-resistant lung cancer cells. Wound healing assay was used to observe the migration ability of fucoidan to inhibit drug-resistant lung cancer cell lines, and the expression of MMP in drug-resistant lung cancer cells treated with fucoidan was detected by gelatin zymography assay. DNA fragmentation assay and apoptosis assay were confirmed whether fucoidan to induce the apoptosis pathway of drug-resistant lung cancer cells, the expression of the resistance-related gene sorcin and the autophagy-related genes LC3 and Beclin-1 and the proliferation-related gene β-catenin in drug-resistant lung cancer cells were detected by RT-PCR. Western blot analysis was confirmed whether fucoidan induced drug-resistant lung cancer cells to express the proliferation-related protein β-catenin.
Result: MTT assay was shown that fucoidan indeed can synergize with doxorubicin increase sensitivity of drug-resistant lung cancer cells. Wound healing assay also was observed that fucoidan synergizes increased the ability of doxorubicin to inhibit the migration of drug-resistant lung cancer cells, and through DNA fragmentation assay and apoptosis assay was observed that fucoidan synergizes with doxorubicin induce increased apoptosis. Gelatin zymography assay was demonstrated that fucoidan synergizes doxorubicin inhibited expression of MMP-9. It was also demonstrated by RT-PCR that fucoidan synergizes with doxorubicin inhibited the expression of LC3 and Beclin-1. Western blot analysis was confirmed that fucoidan synergizes doxorubicin reached the death of drug-resistant lung cancer cells by inhibiting β-catenin.
Conclusion: Fucoidan can enhance doxorubicin to inhibit drug-resistant lung cancer cells, inhibiting cell migration by decreasing the expression of MMP-9, increasing apoptosis of induction, and inhibiting autophagy in drug-resistant lung cancer cells, and inhibiting the proliferation of drug- resistant lung cancer cells by decreasing β-catenin.
| Identifer | oai:union.ndltd.org:TW/107FYU00108012 |
| Date | January 2019 |
| Creators | WANG, YU-CHIEN, 王宇茜 |
| Contributors | TSAO, DER-AN, 曹德安 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 76 |
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