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通过水飞蓟宾联合治疗使重组人肿瘤坏死因子相关凋亡诱导配体耐药的三阴性乳腺癌致敏

Sensitization of rhTRAIL-resistant Triple-negative Breast Carcinoma Through Silibinin Co-Treatment.

作者信息

Manouchehri Jasmine M, Kalafatis Michael

机构信息

Department of Chemistry, Science and Research Center, Cleveland State University, Cleveland, OH, U.S.A.

Center for Gene Regulation in Health and Disease (GRHD), Cleveland State University, Cleveland, OH, U.S.A.

出版信息

Anticancer Res. 2017 Dec;37(12):6593-6599. doi: 10.21873/anticanres.12116.

Abstract

BACKGROUND/AIM: Triple-negative breast cancer (TNBC) is the most fatal form of breast cancer due to the shortcomings of therapies. However, recombinant human tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL) is a promising anticancer therapeutic that possesses the capability to promote the induction of apoptosis in cancer cells, but some TNBCs are resistant to rhTRAIL's pro-apoptotic effects. Therefore, a combinatorial treatment approach with silibinin and rhTRAIL was considered in order to sensitize rhTRAIL-resistant TNBCs.

MATERIALS AND METHODS

The co-treatment of rhTRAIL and silibinin's impact on apoptosis induction in rhTRAIL-resistant TNBC BT-20 and HCC1937 cells was inspected via application of Annexin V/PI assays and western blot analysis.

RESULTS

Silibinin possessed the ability to sensitize the examined rhTRAIL-resistant TNBC cells to rhTRAIL-induced apoptosis through the up-regulation of death receptors 4 and 5 and the down-regulation of survivin transcriptionally.

CONCLUSION

Silibinin is a good sensitizing agent for rhTRAIL-resistant TNBCs.

摘要

背景/目的:三阴性乳腺癌(TNBC)由于治疗方法的缺陷,是最致命的乳腺癌形式。然而,重组人肿瘤坏死因子相关凋亡诱导配体(rhTRAIL)是一种有前景的抗癌治疗药物,具有促进癌细胞凋亡诱导的能力,但一些TNBC对rhTRAIL的促凋亡作用具有抗性。因此,考虑采用水飞蓟宾与rhTRAIL联合治疗的方法,以使对rhTRAIL耐药的TNBC细胞敏感。

材料与方法

通过应用膜联蛋白V/碘化丙啶(Annexin V/PI)检测法和蛋白质印迹分析,考察rhTRAIL与水飞蓟宾联合处理对rhTRAIL耐药的TNBC细胞系BT-20和HCC1937细胞凋亡诱导的影响。

结果

水飞蓟宾能够通过转录上调死亡受体4和5以及下调生存素,使所检测的对rhTRAIL耐药的TNBC细胞对rhTRAIL诱导的凋亡敏感。

结论

水飞蓟宾是一种对rhTRAIL耐药的TNBC有效的增敏剂。

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