Anticancer Res：揭示乳腺癌潜在的联合治疗方法

近日，来自波士顿大学的研究者阐释了一种体外乳腺癌细胞有效的联合治疗方法，相关研究成果刊登在了近日的国际杂志Anticancer Research上。在美国乳腺癌是妇女常见的一种癌症，而且乳腺癌也是导致女性死亡的主要原因。三阴性乳腺癌占到了所有乳腺癌发病病例的14%-20%，这种疾病主要是患者机体的癌细胞缺少激素受体，包括HER-2等。三阴性乳腺癌通常在美国和非洲妇女身上高发，而且复发率高、致死率高。

文章中，研究者在体外检测了使用外基因药物（epigenetic drug）和蛋白酶抑制剂来作用于乳腺癌细胞，这种联合疗法激素敏感型的。研究者同时也使用组蛋白脱乙酰基酶抑制剂和钙蛋白酶抑制剂来进行试验。研究中研究者发现了通过诱导细胞周期停滞使得癌症细胞生长抑制和通过诱导细胞死亡以达到增加癌症细胞死亡的方法，然而研究者表示，这种联合疗法抑制癌症细胞的机制是不同的，激素敏感性的细胞可以在早期阻止细胞周期的发生。对于三阴性乳腺癌细胞来说，抑制剂允许标记肿瘤抑制基因ARHI，使其再表达，这将有效帮助阻止癌症细胞的生长并且使得癌细胞死亡。

目前研究者的研究结果提供了一种模型，通过这种模型我们可以调查肿瘤抑制基因的重新表达等功能。当然这项研究需要深入进行开展下去，不过研究者表示，他们的研究成果对于治疗乳腺癌患者来说会有一定的借鉴意义。

编译自：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.