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      今日廣東 廣州 深圳 珠海 汕頭 佛山 韶關 湛江 肇慶 江門 茂名 惠州 梅州 汕尾 河源 陽江 清遠 東莞 中山 潮州 揭陽 云浮
      新粵網 > 廣東 > 今日廣東 > 正文

      廣東醫科大學揭示怡萊霉素C抗三陰乳腺癌的作用機制

      來源:廣東科技報 2019-07-05 14:38   http://www.e88p.com/

      本報訊(記者蔡敏霞通訊員謝孝東)近日,廣東醫科大學張華副教授課題組在血液和腫瘤學領域權威雜志JournalofHematology&Oncology上以廣東醫科大學為第一單位在線發表了和中科院南海海洋研究所合作的研究論文“IlamycinCinducesapoptosisandinhibitsmigrationandinvasionintriple-negativebreastcancerbysuppressingIL-6/STAT3pathway.JHematolOncol.2019;12(1):60”,揭示了從深海放線菌中分離的結構新穎、具有較強抗腫瘤活性的怡萊霉素C(IlamycinC)的抗三陰乳腺癌作用機制。

      據了解,三陰乳腺癌(TNBC)是乳腺癌的一個亞型,相比其他亞型,TNBC易轉移、易復發、易產生耐藥性,死亡率高,整體生存率較差。TNBC的治療手段較少,聯合化療是唯一有效的治療方式,但是這些藥物的毒副作用及耐藥性使其臨床應用受限。目前尚無針對TNBC的系統的治療指南,沒有個體化治療方案。因此,尋找針對TNBC的特異性靶向治療藥物仍然是TNBC臨床治療領域的重要挑戰。

      海洋中蘊藏著豐富的海洋微生物資源,由于深海環境營養匱乏,生活在深海的微生物為了爭奪生存空間,會產生抗生素抑制周邊微生物的生長。因此,目前海洋來源的天然產物及藥物研發已成為國際上的研究熱點。張華課題跟中科院南海海洋研究所合作,發現從深海分離的一系列新穎的Ilamycin家族化合物中幾個Ilamycin化合物具有較好的抗腫瘤活性,廣東醫科大學作為參與單位共同發表在NatureCommunication上。

      據悉,該論文的研究表明,跟臨床化療藥物阿霉素和順鉑相比,Ilamycin家族中的一個化合物IlamycinC對正常細胞的細胞毒活性較小,而且跟其他乳腺癌亞型相比對TNBC更具有選擇性細胞毒活性,這提示了IlamycinC具有可以開發為臨床化療藥物的潛力。進一步的研究表明,IlamycinC可以通過抑制IL-6誘導的STAT3的磷酸化發揮功能。采用慢病毒穩定過表達STAT3可以逆轉IlamycinC對TNBC細胞凋亡、侵襲和轉移的調控,而敲除STAT3則可以增強IlamycinC對TNBC細胞凋亡、侵襲和轉移的調控。最終闡明了IlamycinC可以通過抑制IL-6誘導的STAT3的磷酸化從而降低其細胞核內磷酸化二聚體的水平,進而可以調控下游的caspase凋亡通路而誘導TNBC細胞的凋亡,同時通過調控遷移和侵襲通路而抑制TNBC細胞的遷移和侵襲。這些結果表明IlamycinC可以作為IL-6/STAT3通路新的抑制劑而具有治療TNBC的潛在應用價值,從而為開發有效的治療TNBC的靶向藥物奠定了基礎。

      廣東醫科大學醫學檢驗學院的張華副教授與中科院南海海洋所的鞠建華研究員、馬俊英研究員為本論文共同通訊作者,廣東醫科大學碩士研究生解青與中科院南海海洋所碩士研究生楊志杰為并列第一作者。該工作得到了國家自然科學基金等項目的資助。

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