Department of Medical Biology, Medical Faculty, Ege University, 35100, Izmir, Turkey.
Department of Medical Biology, Medical Faculty, Aydın Adnan Menderes University, 09010, Aydın, Turkey.
Med Oncol. 2021 Nov 15;39(1):12. doi: 10.1007/s12032-021-01611-w.
Colorectal cancer (CRC) is the third most common cancer worldwide. The development of tumor drug resistance is observed in the treatment of CRC. Combinations of anticancer agents are attracting considerable interest in order to overcome drug resistance in CRC. This study aims to investigate the effect of resveratrol and BIBR1532, either alone or in combination, on the cell viability as well as on expression of long non-coding RNAs (LncRNAs) for HT-29 colon adenocarcinoma cells. The cytotoxic effects of resveratrol and BIBR1532 on HT-29 cells were determined using WST-1 test. Flow cytometry was used to determine apoptotic cell death after treatments. Real-Time PCR was used to identify expression of LncRNAs after treatments. LncExpDB and GEPIA2 were used to evaluate expression profiles of LncRNAs, whose expression levels were decreased in HT-29 cells after treatments, in normal tissues and colon adenocarcinoma tumors. IC concentrations of BIBR1532 and resveratrol were found to be 50.81 μM at 48 h and 86.23 μM at 72 h, respectively. Combination index value was 1.07617. BIBR1532, resveratrol, or their combination reduced the cell viability of HT-29 cells. CCAT1, CRNDE, HOTAIR, PCAT1, PVT1, SNHG16 were down-regulated after treatments. In silico analysis revealed that LncRNAs whose expression levels were decreased after treatments were associated with CRC. Resveratrol, BIBR1532, or their combination may have anti-proliferative effect on colorectal cancer cells through repressing expression of LncRNAs that are involved in progression of CRC.
结直肠癌(CRC)是全球第三大常见癌症。在 CRC 的治疗中观察到肿瘤药物耐药性的发展。为了克服 CRC 中的药物耐药性,联合使用抗癌药物引起了相当大的兴趣。本研究旨在探讨白藜芦醇和 BIBR1532 单独或联合使用对 HT-29 结肠腺癌细胞活力以及长链非编码 RNA(LncRNA)表达的影响。使用 WST-1 试验测定白藜芦醇和 BIBR1532 对 HT-29 细胞的细胞毒性作用。使用流式细胞术测定处理后细胞凋亡。使用实时 PCR 鉴定处理后 LncRNA 的表达。使用 LncExpDB 和 GEPIA2 评估 LncRNA 的表达谱,这些 LncRNA 的表达水平在处理后 HT-29 细胞中降低,在正常组织和结肠腺癌肿瘤中降低。发现 BIBR1532 和白藜芦醇的 IC 浓度分别为 48 小时时的 50.81 μM 和 72 小时时的 86.23 μM。组合指数值为 1.07617。BIBR1532、白藜芦醇或它们的组合降低了 HT-29 细胞的活力。CCAT1、CRNDE、HOTAIR、PCAT1、PVT1、SNHG16 在处理后下调。计算机分析表明,处理后表达水平降低的 LncRNA 与 CRC 相关。白藜芦醇、BIBR1532 或它们的组合可能通过抑制参与 CRC 进展的 LncRNA 的表达对结直肠癌细胞具有抗增殖作用。