LB113:奥拉帕尼对乳腺肿瘤细胞系PARP-1表达的调控作用

M. Moschetta-Pinheiro, Jucimara Colombo, Murilo de Souza Tuckumantel, Gabriela Karam Rebolho, D. A. P. Zuccari
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引用次数: 0

摘要

导读:乳腺癌是妇女中最常见的肿瘤类型,死亡率高,这与疾病发现较晚和由于对方案治疗产生耐药性而导致治疗失败有关。众所周知,多种抗肿瘤药物能够通过激活DNA修复途径诱导化疗耐药。其中,parp参与单链断裂的识别和修复。因此,诸如PARP抑制剂(olaparib)之类的新药物正在被研究作为癌症的潜在治疗靶点,作为逃避肿瘤细胞对化疗药物(如铂盐类药物)耐药性的替代方案。在此背景下,本研究的目的是评估奥拉帕尼治疗后PARP在乳腺肿瘤细胞系中的表达。材料与方法:乳腺肿瘤细胞系MDA-MB-468和CF41在DMEM高糖培养基中培养,37℃,5% CO2。不同浓度卡铂处理后,用MTT法测定细胞活力。卡铂和奥拉帕尼浓度分别为10µM和10µM后,分别用免疫荧光和实时PCR检测PARP-1蛋白和基因的表达。结果:不同浓度卡铂处理24h后细胞活力明显降低。卡铂和奥拉帕尼治疗后,PARP-1蛋白和基因表达均显著降低。在某些情况下,联合用药可增强治疗效果。结论:奥拉帕尼对人、犬乳腺癌细胞中PARPs激活的DNA修复机制有一定的调控作用。引文格式:Marina Gobbe Moschetta-Pinheiro, juucimara Colombo, Murilo de Souza Tuckumantel, Gabriela Karam Rebolho, Debora aprecida Zuccari。奥拉帕尼对乳腺肿瘤细胞系中PARP-1表达的调控[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志,2021;81(13 -增刊):摘要nr LB113。
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Abstract LB113: Regulation of PARP-1 expression in mammary tumor cell lines after treatment with olaparib
Introduction: Breast cancer is the most common tumor type among women and has a high mortality rate, which is associated with late detection of the disease and treatment failure due to the acquisition of resistance to protocol treatments. It is known that a variety of antitumor drugs are capable of inducing chemoresistance by activating DNA repair pathways. Among these, the PARPs are involved in the recognition and repair of simple-strand breaks. As a consequence, new drugs such as PARP inhibitors (olaparib), are being investigated as potential therapeutic targets in cancer, as an alternative to evade the resistance of tumor cells to chemotherapeutic agents, such as those in the class of platinum salts. In this context, the aim of this study was to evaluate the PARP expression after olaparib tratament with in mammary tumor cell lines. Materials and Methods: Mammary tumor cell lines MDA-MB-468 and CF41 was cultured in DMEM high glucose culture medium, at 37°C in 5% CO2. Cell viability was measured by MTT assay after treatment with different concentrations of carboplatin. Once stablished the concentration of 10µM for carboplatin and 10µM of olaparib, the protein and gene expression of PARP-1 were detected by immunofluorescence and real time PCR, respectively. Results: There was a significantly decrease of cell viability after treatment with different concentrations of carboplatin in 24 hours. Both PARP-1 protein and gene expression significantly decreased after treatment with carboplatin and olaparib. In some cases, the treatment action was potentiated when performed in combination. Conclusion: Our results suggest the efficacy of olaparib in controlling the mechanism of DNA repair activated by PARPs in human and canine breast cancer cells. Citation Format: Marina Gobbe Moschetta-Pinheiro, Jucimara Colombo, Murilo de Souza Tuckumantel, Gabriela Karam Rebolho, Debora Aparecida Zuccari. Regulation of PARP-1 expression in mammary tumor cell lines after treatment with olaparib [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB113.
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