近日，來(lái)自波士頓大學(xué)的研究者闡釋了一種體外乳腺癌細(xì)胞有效的聯(lián)合治療方法,，相關(guān)研究成果刊登在了近日的國(guó)際雜志Anticancer Research上。在美國(guó)乳腺癌是婦女常見(jiàn)的一種癌癥,，而且乳腺癌也是導(dǎo)致女性死亡的主要原因,。三陰性乳腺癌占到了所有乳腺癌發(fā)病病例的14%-20%，這種疾病主要是患者機(jī)體的癌細(xì)胞缺少激素受體,，包括HER-2等,。三陰性乳腺癌通常在美國(guó)和非洲婦女身上高發(fā)，而且復(fù)發(fā)率高,、致死率高,。
文章中，研究者在體外檢測(cè)了使用外基因藥物（epigenetic drug）和蛋白酶抑制劑來(lái)作用于乳腺癌細(xì)胞,，這種聯(lián)合療法激素敏感型的,。研究者同時(shí)也使用組蛋白脫乙酰基酶抑制劑和鈣蛋白酶抑制劑來(lái)進(jìn)行試驗(yàn),。研究中研究者發(fā)現(xiàn)了通過(guò)誘導(dǎo)細(xì)胞周期停滯使得癌癥細(xì)胞生長(zhǎng)抑制和通過(guò)誘導(dǎo)細(xì)胞死亡以達(dá)到增加癌癥細(xì)胞死亡的方法,，然而研究者表示，這種聯(lián)合療法抑制癌癥細(xì)胞的機(jī)制是不同的,，激素敏感性的細(xì)胞可以在早期阻止細(xì)胞周期的發(fā)生,。對(duì)于三陰性乳腺癌細(xì)胞來(lái)說(shuō)，抑制劑允許標(biāo)記腫瘤抑制基因ARHI,，使其再表達(dá),，這將有效幫助阻止癌癥細(xì)胞的生長(zhǎng)并且使得癌細(xì)胞死亡。
目前研究者的研究結(jié)果提供了一種模型,，通過(guò)這種模型我們可以調(diào)查腫瘤抑制基因的重新表達(dá)等功能,。當(dāng)然這項(xiàng)研究需要深入進(jìn)行開(kāi)展下去，不過(guò)研究者表示,，他們的研究成果對(duì)于治療乳腺癌患者來(lái)說(shuō)會(huì)有一定的借鑒意義,。（生物谷Bioon.com）
編譯自：In Vitro Study Identifies Potential Combination Therapy for Breast Cancer
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Anti-breast Cancer Effects of Histone Deacetylase Inhibitors and Calpain Inhibitor
MEGAN A. MATAGA, SHOSHANA ROSENTHAL, SARAH HEERBOTH, AMRITA DEVALAPALLI, SHANNON KOKOLUS, LEAH R. EVANS, MCKENNA LONGACRE, GENEVIEVE HOUSMAN and SIBAJI SARKAR⇓
Development of new breast cancer therapies is needed, particularly as cells become refractory or develop increased drug resistance. In an effort to develop such treatments, class I and II histone deacetylases (HDACs), alone and in combination with other cytotoxic agents, are currently in clinical trial. Herein, we discuss the effects of histone deacetylase inhibitors (HDACi) when used in combination with calpeptin, an inhibitor of the regulatory protease, calpain. We present results of study in two breast cancer cells lines with distinct characteristics: MDA-MB-231 and MCF-7. When used in combination with calpeptin, two chemically distinct HDACi significantly inhibited growth and increased cell death by inducing cell-cycle arrest and apoptosis. MCF-7 cells exhibited a greater proportion of arrest at the G1 phase, whereas triple-negative MDA-MB-231 cells exhibited increased cell cycle arrest at the S phase. Methylation of the imprinted and silenced proapoptoic tumor suppressor gene aplasia Ras homolog member I (ARHI) was reduced in both cell lines after treatment with HDACi. However, it was only re-expressed on such treatment in MDA-MB-231 cells, suggesting that re-expression operates under differential mechanisms in these two cell lines. Collectively, these results showed that the combination of HDACi and calpeptin inhibited the growth of two distinctly different types of breast cancer cells and could have wide clinical applications, though the mechanisms of inhibition are possibly different.
