Heteronemin and Tetrac Induce Anti-proliferation by Blocking EGFR- mediated Signaling in Colorectal Cancer Cells

Taipei Medical University Institutional Repository > 醫學科技學院 > 癌症生物學與藥物研發博士學位學程 > 博碩士論文 > Item 987654321/63247

請使用永久網址來引用或連結此文件: http://libir.tmu.edu.tw/handle/987654321/63247

題名:	Heteronemin and Tetrac Induce Anti-proliferation by Blocking EGFR- mediated Signaling in Colorectal Cancer Cells
作者:	UNSON, SUKANYA
貢獻者:	癌症生物學與藥物研發博士學位學程林宏惲彭汪嘉康李文山
關鍵詞:	HETERONEMIN;TETRAC;EGFR SIGNALING
日期:	2023-01-12
上傳時間:	2023-12-07 10:18:57 (UTC+8)
摘要:	The mutations in KRAS can be found in 30%~40% of colorectal cancer (CRC) patients. Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies are effective only in CRC patients with KRAS wild-type (WT) status. To discover new therapeutic strategies urgently need for colorectal cancer patients. Sponge extract, heteronemin, has been exerted antitumor effect against several cancer types but not in colorectal cancers. Thyroid hormone analogue, Tetraiodothyroacetic acid (tetrac) has been shown to suppress Ras-mutant cancer cell growth. This study intended to explore the combined inhibitory effect of heteronemin and tetrac, and also its molecular mechanism(s) of action in HT-29 cells (KRAS WT cells) and HCT-116 cells (KRAS MT cells). Cell viability was investigated using a CyQUANT® cell proliferation assay. Protein expressions levels and the percentages of a cell population in the different phases of the cell cycle were respectively determined by Western blotting and flow cytometry. Gene expression profiles were detected by NanoString technology as well as RT-qPCR. Heteronemin in combination with tetrac suppressed the growth of mutant and wild-type KRAS CRC cells. Its combination also caused sub-G1 and S phases cell cycle arrest in both cell lines. In KRAS MT cells, heteronemin combined tetrac downregulated genes involved in cancer progression such as EGFR and decreased cell motility by Nanostring technology. The combination treatment exhibited the inhibition of EGFR signaling through the reduction of phosphorylated ERK1/2 protein expressions in both CRC cell lines. Besides, inactivation of phosphorylated and total PI3K protein were induced by combined treatment in KRAS WT cells. Furthermore, PD-L1 protein levels were decreased after treated KRAS WT cells with tetrac, whereas its expression was downregulated by heteronemin combined tetrac in KRAS MT cells. Hence, tetrac enhances the antitumor effect of heteronemin, and its combination might be a potential candidate for the treatment of CRC to overcome KRAS mutation-acquired resistance to anti-EGFR therapy.
描述:	博士指導教授:林宏惲共同指導教授:彭汪嘉康共同指導教授:李文山委員:劉逸軒委員:李文山委員:邱賢忠委員:皇甫維君委員:陳忻怡委員:黃雯華委員:林宏惲
資料類型:	thesis
顯示於類別:	[癌症生物學與藥物研發博士學位學程] 博碩士論文

文件中的檔案:

檔案	描述	大小	格式	瀏覽次數
index.html		0Kb	HTML	83	檢視/開啟

檢視Licence

在TMUIR中所有的資料項目都受到原著作權保護.

TAIR相關文章

資料載入中.....