Erastin联合Tubacin促进乳腺癌HCC38细胞死亡

Erastin plus Tubacin Treatment Promotes Breast Cancer Cell Death of HCC38

摘要: 目的：根据表观遗传特征，可以对恶性肿瘤进行分型，并针对分子异常代谢给予精准打击，实现抗肿瘤目的，这是一种新兴治疗策略。在多数细胞恶变过程中，胱氨酸的成瘾是常见的异常代谢。随后，Erastin被研究者发现，它能抑制胱氨酸谷氨酸转运体(Xc-system)，从而诱导细胞死亡。对大多数乳腺癌效果显著。然而，三阴型乳腺癌细胞是非间充质的，对Erastin治疗无反应。为了克服这种耐药性，我们筛选并鉴定出Tubacin，它可以转变恶性肿瘤的胱氨酸不敏感的状态。为了验证Tubacin实际效果，我们尝试在Tubacin、Erastin条件下处理三阴型乳腺癌细胞，对比观察细胞死亡实际情况。方法：本研究的三阴型乳腺癌细胞株HCC38购自ATCC公司，在DMSO、Tubacin、Erastin、及Erastin联合Tubacin条件下进行处理，以流式细胞学等方式检测细胞死亡。结果：1) 单独使用Tubaicn、Erastin处理HCC38细胞，细胞死亡幅度无明显变化。2) Erastin联合Tubacin处理癌细胞可以显著诱导死亡。3) 与DMSO、Tub、Era相比，Era + Tub组别细胞死亡明显增多。4) 与DMSO相比，Tub、Era、Era + Tub组别细胞的活性氧均不同程度增高，后两者显著增高。结论：Erastin联合Tubacin可促进乳腺癌HCC38细胞死亡。

Abstract: Purpose: According to epigenetic features, malignant tumors can be typed and given a precise blow against the molecular aberrant metabolism, achieving antitumor purpose, which is an emerging therapeutic strategy. Addiction to cystine is the more common aberrant metabolism involved in most cellular malignant transformation. Subsequently, the cystine blocker erastin was discovered to inhibit the cystine glutamate transporter (XC-System), which induces cell death and has pro-duced significant effect against most breast cancers. However, TNBC cells are non mesenchymal and do not respond to cystine deprivation treatment. To overcome this resistance, we screened and identified tubacin, which can transform the cystine insensitive state of malignancies. To verify the actual effect of tubacin, we tried to treat triple negative breast cancer cells under tubacin, erastin conditions and observed the cell death reality comparatively. Methods: The triple negative breast cancer cell line HCC38 from this study was purchased from ATCC and treated in DMSO, Tubacin, Erastin, and Erastin plus Tubacin to detect cell death by flow cytometry. Results: 1) In HCC38 cells treated with tubaicn or erastin alone, the magnitude of cell death was unchanged. 2) Treatment of cancer cells with erastin in combination with tubacin significantly induced death. 3) Compared with DMSO, Tub, or Era, cell death was significantly increased in the Erastin plus Tubacin Group. 4) Compared with DMSO, ROS increased in all cell lines in the Tub, Era, and Erastin plus Tubacin groups, and the latter two were significantly higher. Conclusions: Erastin, in combination with tuba-cin, confers breast cancer cells death of HCC38.