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Please use this identifier to cite or link to this item: http://ntour.ntou.edu.tw:8080/ir/handle/987654321/53551

Title: 豆科植物粗萃物及化合物對乳癌的藥理作用與機制
Pharmacological and mechanistic studies of Leguminosae plant extracts and compounds for breast cancer
Authors: Ho, Sing-Zong
何欣容
Contributors: NTOU:Department of Aquaculture
國立臺灣海洋大學:水產養殖學系
Keywords: 乳癌;豆科植物;抗細胞增生;誘導細胞凋亡;檢查點機酶;MCF-7乳癌模式鼠;免疫組織染色
Breast cancer;Leguminosae family;anti-proliferation;apoptosis;checkpoint kinases;MCF-7 tumor-bearing mice;immunohistochemistry
Date: 2019
Issue Date: 2020-07-03T08:30:23Z
Abstract: 根據世界衛生組織的調查,乳癌每年約新增200多萬的病例,並造成60多萬人死亡,是好發於女性的惡性腫瘤之一。目前的治療方式,主要是以外科手術搭配化學藥物進行治療。臨床上,轉移性乳癌仍無法有效地根治,且在治療後復發率仍相當高,因此開發針對乳癌早期診斷與治療的新穎療法為非常重要的課題。一直以來,植物為抗癌化學藥物的重要來源。研究發現,豆科植物不但能提供人體所需之植物性蛋白及維生素,其萃取物更有抗發炎、抗腫瘤等功效。透過楊文欽老師與林雅俐老師實驗室所建立的生物活性為導向之篩選平台找出能有效抗癌的豆科植物「PC」,並透過高效液相層析 (high performance liquid chromatography, HPLC)找出其活性化合物 (bioactivity compounds, Cpds)。細胞實驗發現,PC之粗萃物 (CE)及兩種化合物Cpd4及Cpd7顯示其有抑制癌細胞分裂、造成DNA損傷,進而促進細胞凋亡之效果,因此。本研究將延續細胞實驗結果,以乳癌模式鼠作為研究平臺,探討PC對於乳癌的影響。利用將冷光 (Luciferase)基因轉入人類乳癌細胞MCF-7中,建立MCF-7冷光乳癌模式鼠並評估CE、Cpd4、Cpd7之抗腫瘤藥效。結果顯示,在分別給予乳癌化療藥:太平洋紫杉醇 (Paclitaxel, PTX 5 mg/kg)、不同濃度之CE及Cpds四週後,各組別MCF-7荷瘤小鼠之腫瘤大小皆隨著藥物濃度的增加,而顯著地受到抑制,且CE及Cpds皆能延長其存活天數。且經由免疫組織染色實驗,結果顯示CE及Cpds可有效地抑制細胞增生,並促進癌細胞凋亡的比例,這實驗結果與先前細胞實驗一致,其中Cpd4透過抑制檢查點激酶 (Checkpoint kinases, CHK1,CHK2)達到抑制細胞增生的效果,而Cpd7及CE的促進細胞凋亡則與促進檢查點激酶有正相關,最後發現雖然Cpd4及Cpd7兩化合物的作用機制不同,Cpd4與Cpd7的複合治療效果優於單一化合物治療,而所有結果皆證實PC粗萃物及其化合物可有效在動物實驗上抑制腫瘤生長,有成為新標靶藥物的潛力。
According to the published data of World Health Organization (WHO), the annual new cases of breast cancer are about 2 million people and the death of breast cancer 600 thousand every year, which make breast cancer a leading cause of death in women. Surgery and chemical treatment are known as the main therapy of breast cancer. However, the metastasis of breast cancer is still incurable, and the recurrence rate after therapy in patients is high. Thus, development of new therapeutic or preventive agents for breast cancer becomes very important. The phytochemicals in anticancer drug development have been studied for long time. The Leguminosae family plants are not only the important sources of vegetable protein and vitamin, the compounds of the plant also contain anti-inflammation and anti-tumor activities. Our lab previously demonstrated that the crude extra (CE) and active compounds (Cpds) of PC from the Leguminosae family plants are able to inhibit the proliferation and induce the apoptosis of tumor cells. We further pursuit the anti-tumor effect of this plant in cancer cell-bearing mice model. To build a luciferase-expressing breast cancer mouse model, we transduced the luciferase gene into MCF-7 cells. Next, the CE and Cpds of PC were injected to MCF-7-Luc tumor-bearing mice for 4 weeks. We found that CE and Cpds prolonged the survival days of mice and inhibited the expression of luciferase and tumor cell growth in a dose manner. The immunohistochemistry data also indicated that CE and Cpds showed the anti-proliferative effect on tumor cells. Cpd4 suppressed the growth of tumor by inhibiting the activation of checkpoint kinases (CHK1 and CHK2). In contrary, Cpd7 and CE up-regulated the activation of checkpoint kinases. Moreover, combination of Cpd4 and Cpd7 showed the effective anti-tumor effect in vivo. In conclusion, CE and Cpds as potential chemotherapy medicine against cancer are thus warranted.
URI: http://ethesys.lib.ntou.edu.tw/cgi-bin/gs32/gsweb.cgi?o=dstdcdr&s=G0010633027.id
http://ntour.ntou.edu.tw:8080/ir/handle/987654321/53551
Appears in Collections:[水產養殖學系] 博碩士論文

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