Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Department of Biology, School of Basic Science, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Mol Biol Rep. 2024 Mar 14;51(1):420. doi: 10.1007/s11033-024-09339-2.
Although extensive efforts have been made to improve the treatment of colorectal cancer (CRC) patients, the prognosis for these patients remains poor. A wide range of anti-cancer agents has been applied to ameliorate the clinical management of CRC patients; however, drug resistance develops in nearly all patients. Based on the prominent role of PI3K/AKT signaling in the development of CRC and current interest in the application of PI3K inhibitors, we aimed to disclose the exact mechanism underlying the efficacy of BKM120, a well-known pan-class I PI3K inhibitor, in CRC-derived SW480 cells.
The effects of BKM120 on SW480 cells were studied using MTT assay, cell cycle assay, Annexin V/PI apoptosis tests, and scratch assay. In the next step, qRT-PCR was used to investigate the underlying molecular mechanisms by which the PI3K inhibitor could suppress the survival of SW480 cells.
The results of the MTT assay showed that BKM120 could decrease the metabolic activity of SW480 cells in a concentration and time-dependent manner. Investigating the exact mechanism of BKM120 showed that this PI3K inhibitor induces its anti-survival effects through a G2/M cell cycle arrest and apoptosis-mediated cell death. Moreover, the scratch assay demonstrated that PI3K inhibition led to the inhibition of cancer invasion and inhibition of PI3K/AKT signaling remarkably sensitized SW480 cells to Cisplatin.
Based on our results, inhibition of PI3K/AKT signaling can be a promising approach, either as a single modality or in combination with Cisplatin. However, further clinical studies should be performed to improve our understanding.
尽管已经做出了广泛的努力来改善结直肠癌（CRC）患者的治疗效果，但这些患者的预后仍然不佳。已经应用了广泛的抗癌药物来改善 CRC 患者的临床管理，但几乎所有患者都会产生耐药性。鉴于 PI3K/AKT 信号通路在 CRC 发展中的重要作用，以及当前对应用 PI3K 抑制剂的兴趣，我们旨在揭示知名的泛 I 类 PI3K 抑制剂 BKM120 在 CRC 衍生的 SW480 细胞中疗效的确切机制。
通过 MTT 检测、细胞周期检测、Annexin V/PI 凋亡检测和划痕实验研究 BKM120 对 SW480 细胞的影响。下一步，通过 qRT-PCR 研究 PI3K 抑制剂抑制 SW480 细胞存活的潜在分子机制。
MTT 检测结果表明，BKM120 可以浓度和时间依赖性方式降低 SW480 细胞的代谢活性。研究 BKM120 的确切机制表明，这种 PI3K 抑制剂通过 G2/M 细胞周期阻滞和凋亡介导的细胞死亡来发挥其抗生存作用。此外，划痕实验表明，PI3K 抑制导致癌症侵袭抑制，并且显著增加 SW480 细胞对顺铂的敏感性。
基于我们的结果，抑制 PI3K/AKT 信号通路可以是一种有前途的方法，无论是单独应用还是与顺铂联合应用。然而，应该进行进一步的临床研究来加深我们的理解。
