Orzechowska Emilia Joanna, Girstun Agnieszka, Staron Krzysztof, Trzcinska-Danielewicz Joanna
Department of Molecular Biology, Institute of Biochemistry, Faculty of Biology, University of Warsaw, 02-096 Warsaw, Poland.
Oncol Rep. 2015 May;33(5):2143-50. doi: 10.3892/or.2015.3841. Epub 2015 Mar 9.
Overexpression of the BH3-interacting domain death agonist (BID) protein sensitizes certain cancer cell lines to apoptosis induced by anticancer agents, particularly by those acting through death receptors (e.g. TRAIL). Previously, we showed that recombinant BID fused with TAT cell penetrating peptide (TAT-BID) allowed for controlled delivery of BID to different cancer cell lines and moderately sensitized some of them to TRAIL or slightly to camptothecin. In the present study, we showed that TAT-BID delivered to HeLa cells strongly sensitized them to doxorubicin, as identified by cell viability and apoptosis assays. Another cell line sensitized to doxorubicin was PC3, whereas A549 and LNCaP cells were sensitized moderately or not at all, respectively. Sensitization was more pronounced at 1 µM doxorubicin administered for 48 h than for lower doses and shorter treatments. TAT-BID and doxorubicin may thus be considered as a potential therapeutic combination for cervical carcinoma and advanced prostate cancer treatment.
BH3相互作用结构域死亡激动剂（BID）蛋白的过表达使某些癌细胞系对抗癌药物诱导的凋亡敏感，尤其是对那些通过死亡受体起作用的药物（如TRAIL）。此前，我们表明与TAT细胞穿透肽融合的重组BID（TAT-BID）能够将BID可控地递送至不同的癌细胞系，并使其中一些细胞系对TRAIL适度敏感，或对喜树碱轻度敏感。在本研究中，通过细胞活力和凋亡检测发现，递送至HeLa细胞的TAT-BID使其对阿霉素强烈敏感。另一个对阿霉素敏感的细胞系是PC3，而A549和LNCaP细胞分别对阿霉素中度敏感或完全不敏感。在给予1μM阿霉素处理48小时时，敏感性比低剂量和短时间处理更为明显。因此，TAT-BID和阿霉素可被视为宫颈癌和晚期前列腺癌治疗的潜在治疗组合。
