Temozolomide Enhances Triple-Negative Breast Cancer Virotherapy In Vitro.
Temozolomide Enhances Triple-Negative Breast Cancer Virotherapy In Vitro.
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DOI：
10.3390/cancers10050144
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发表时间：
2018-05-17
期刊：
影响因子：
5.2
通讯作者：
Gomez-Gutierrez JG
中科院分区：
文献类型：
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作者：
Garza-Morales R;Gonzalez-Ramos R;Chiba A;Montes de Oca-Luna R;McNally LR;McMasters KM;Gomez-Gutierrez JG
三阴性乳腺癌（TNBC）是最具侵袭性的癌症之一，治疗仅限于化疗和放疗。溶瘤病毒治疗可能是一种很有前途的治疗TNBC的方法。然而，基于溶瘤腺病毒（OAd）的单治疗临床试验结果并不乐观。化疗诱导的自噬可以增加OAd的效力，自噬是一种细胞内降解系统，将细胞质成分传递给溶酶体。本研究评估了烷基化剂替莫唑胺（TMZ）诱导的自噬增加TNBC细胞OAd复制和溶瘤的能力。用在病毒衣壳上表达红色荧光蛋白mCherry （OAdmCherry）的OAd单独或与TMZ联合感染人TNBC MDA-MB-231和HCC1937细胞和小鼠4T1细胞。与OAdmCherry或TMZ单独处理的TNBC细胞相比，OAdmCherry/TMZ处理的TNBC细胞显示出更高的mCherry和腺病毒（Ad）早期1A区（E1A）表达和增强的癌细胞杀伤。联合治疗介导的细胞死亡与病毒复制和自噬标记物轻链3 (LC3)-II的积累有关。总的来说，本研究提供了TMZ在人和小鼠TNBC细胞中增加溶瘤病毒治疗能力的实验证据。
Triple-negative breast cancer (TNBC) is one of the most aggressive types of cancer, and treatment is limited to chemotherapy and radiation. Oncolytic virotherapy may be a promising approach to treat TNBC. However, oncolytic adenovirus (OAd)-based mono-therapeutic clinical trials have resulted in modest outcomes. The OAd potency could be increased by chemotherapy-induced autophagy, an intracellular degradation system that delivers cytoplasmic constituents to the lysosome. In this study, the ability of alkylating agent temozolomide (TMZ)-induced autophagy to increase OAd replication and oncolysis in TNBC cells was evaluated. Human TNBC MDA-MB-231 and HCC1937 cells and mouse 4T1 cells were infected with an OAd expressing the red fluorescent protein mCherry on the virus capsid (OAdmCherry) alone or in combination with TMZ. TNBC cells treated with OAdmCherry/TMZ displayed greater mCherry and adenovirus (Ad) early region 1A (E1A) expression and enhanced cancer-cell killing compared to OAdmCherry or TMZ alone. The combined therapy-mediated cell death was associated with virus replication and accumulation of the autophagy marker light chain 3 (LC3)-II. Overall, this study provides experimental evidence of TMZ’s ability to increase oncolytic virotherapy in both human and murine TNBC cells.
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影响因子：
7.2
作者：
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通讯作者：
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影响因子：
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45.3
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通讯作者：
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影响因子：
6.4
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