以整合素αvβ3受體為靶向潛在治療乳癌的研究

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題名:	以整合素αvβ3受體為靶向潛在治療乳癌的研究 Targeting Integrin αvβ3 for Potential Breast Cancer Treatment
作者:	陳昱均 CHEN, YU-CHUN
貢獻者:	藥學系碩士班林淑娟
關鍵詞:	整合素αvβ3受體;黃體素;乳癌;三陰性乳癌 Integrin αvβ3;Progesterone;Breast Cancer;Triple-Negative Breast Cancer
日期:	2022-08-11
上傳時間:	2023-01-18 10:34:49 (UTC+8)
摘要:	乳癌是全球女性最常被診斷出的癌症，是癌症第二大死亡的原因，每年病例都在增加。三陰性乳癌（TNBC）是侵襲性乳癌中主要的亞型，特點是雌激素受體 (ER)、人類表皮生長因子受體 2 (HER2) 和黃體素受體 (PR) 表現不足。目前，由於化療方案毒性高，且三陰性乳癌的治療藥物選擇有限，預後差，且復發率高，通常無法治愈。儘管癌症靶向藥物多有進展，但TNBC 的治療仍然是當今臨床上的一項重大挑戰。在各種癌細胞、有效生長的內皮細胞和骨細胞中都有整合素 αvβ3受體的表現，除了具有 RGD 序列的分子外，一些小分子都已被證明可與整合素 αvβ3受體結合。除甲狀腺激素外，雌激素和雄性激素都在與RGD結合域結合後刺激癌細胞的生長。但是，當白藜蘆醇與癌細胞 RGD 結合域結合，活化訊號並阻抗癌細胞的增生。黃體素通過黃體素受體 (PR)結合後，誘導基因表現，已被證明可抑制 PR 陽性的乳癌細胞增生。然而，實驗的結果顯示，黃體素卻能活化PR陰性乳癌細胞中的增生基因的表現。目前對於黃體素與整合素αvβ3受體的調節訊號路徑作用尚未充分了解；為了證實黃體素能刺激PR陰性乳癌細胞的增生，但對PR陽性乳癌細胞卻有抑制增生作用，因此藉著抗體或 RGD 胜?來阻斷黃體素與整合素αvβ3受體的結合。實驗結果顯示皆能減少黃體素誘導的訊號傳遞和蛋白質累積，且黃體素誘導的細胞增生作用是隨著實驗條件而變化的。綜合以上，在PR陰性乳癌細胞中，黃體素與整合素αvβ3受體之間關聯性的發現，提供了一個潛在治療三陰性乳癌的新契機。 Breast cancer is the most frequently diagnosed cancer with increasing cases annually and is the second most common cause of cancer mortality in women worldwide. Triple-negative breast cancer (TNBC) is a predominantly aggressive subtype of breast cancer with a poorer prognosis but a higher recurrence rate. TNBC, a type of invasive BC, is characterized by deficiencies in the expression of estrogen (ER), human epidermal growth factor receptor 2 (HER2), and progesterone receptors (PR). Currently, the treatment options for TNBC are limited due to highly toxic chemotherapeutic regimens and typically cannot be cured. Despite the advances in targeted drugs on the market, the treatment of TNBC remains a major challenge in clinical practice today. Integrin αvβ3 expresses in various cancer cells, potent growth endothelial cells, and osteocytes. In addition to molecules with Arg-Gly-Asp tripeptide (RGD) sequences, several small molecules have been shown to bind to integrin αvβ3 as the receptor. In addition to thyroid hormone, estrogen, and androgen are able to bind to RGD binding domain to stimulate cancer cell growth. On the other hand, resveratrol also binds to RGD binding domain to activate cell activities including anti-proliferation in cancer cells. Progesterone via progesterone receptor (PR) induces gene expression. Progesterone has been shown to inhibit cell proliferation in PR-positive breast cancer cells. Results indicated that progesterone activated proliferative gene expression in PR-negative breast cancer cells. However, the role of integrin αvβ3 on progesterone-modulated signal pathways was not fully investigated. Progesterone showed a stimulatory effect on cell proliferation in PR-negative breast cancer cells but an inhibitory effect in PR-positive breast cancer cells. To block integrin αvβ3 binding by antibodies or RGD peptides reduced progesterone-induced signal transduction and protein accumulation. Moreover, the progesterone-induced cell growth was alternated. In summary, the correlation between integrin αvβ3 and progesterone in PR-negative breast cancer cells provides us with a novel therapeutic opportunity in triple-negative breast cancers.
描述:	碩士指導教授：林淑娟委員：林淑娟委員：王莉萱委員：張淑芬
資料類型:	thesis
顯示於類別:	[藥學系] 博碩士論文

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