Rubenstein Marvin, Hollowell Courtney M P, Guinan Patrick
Division of Cellular Biology, Hektoen Institute for Medical Research, Chicago, IL, U.S.A. Division of Urology, Stroger Hospital of Cook County, Chicago, IL, U.S.A. Department of Biochemistry, Rush University Medical Center, Chicago, IL, U.S.A. Department of Urology, Rush University Medical Center, Chicago, IL, U.S.A.
Division of Urology, Stroger Hospital of Cook County, Chicago, IL, U.S.A.
In Vivo. 2014 Sep-Oct;28(5):867-70.
Antisense oligonucleotides have targeted regulatory proteins in both in vivo and in vitro prostate cancer models. We evaluated mono- and bispecific oligonucleotides which targeted and comparably suppressed B-cell lymphoma-2 BCL-2 (an apoptosis-inhibitory protein) expression in LNCaP cells. These oligonucleotides were administered with lipofectin as part of a nanoparticle delivery system. Treated cells compensated by suppressing caspase-3 (an apoptosis promoter) and enhancing expression of the androgen receptor and its co-activating p300 and IL-6 proteins. This suggests a progression to increased androgen sensitivity (in LNCaP) accompanies BCL-2 suppression and a gene activation pattern associated with more advanced prostate tumors. To further evaluate compensatory mechanisms related to tumor resistance in the present study we evaluate the expressed levels of the AKT1 oncogene and STAT3 transcription factor, finding both to be enhanced.
在体内和体外前列腺癌模型中，反义寡核苷酸已靶向调控蛋白。我们评估了单特异性和双特异性寡核苷酸，它们靶向并相当程度地抑制了LNCaP细胞中B细胞淋巴瘤-2（BCL-2，一种凋亡抑制蛋白）的表达。这些寡核苷酸与脂质转染试剂一起作为纳米颗粒递送系统的一部分给药。经处理的细胞通过抑制半胱天冬酶-3（一种凋亡促进剂）并增强雄激素受体及其共激活因子p300和白细胞介素-6蛋白的表达来进行代偿。这表明伴随着BCL-2抑制，雄激素敏感性增加（在LNCaP中）以及与更晚期前列腺肿瘤相关的基因激活模式。为了在本研究中进一步评估与肿瘤耐药相关的代偿机制，我们评估了AKT1癌基因和STAT3转录因子的表达水平，发现两者均增强。
