PDF(Pubmed)
Abstract：
BACKGROUND: This study aims to explore the mechanism of drug resistance in multiple myeloma (MM).
METHODS: In this study, the possible mechanism of chemotherapeutic tolerance was preliminarily explored from two aspects: (I) the changes in cell morphology, cell cycle, cell apoptosis, stem cell markers and the signaling transduction pathway after the irradiation of RPMI-8226 cells; (II) the mechanism of enhancing chemotherapeutic sensitivity through the PI3K/AKT/mTOR signaling pathway.
RESULTS: The results showed that the cell morphology and cell cycle of RPMI-8226 had been significantly changed after receiving a radiation dose of 6 Gy in the logarithmic growth phase, the sensitivity of cells to bortezomib had been decreased, the level of stem cell markers had been upregulated, and the PI3K/AKT/mTOR signaling pathway had been activated. However, blocking the PI3K/AKT/mTOR signaling pathway caused the expression of the stem cell markers of RPMI-8226 cells. In addition, the sensitivity of cells to bortezomib had been increased.
CONCLUSIONS: Blocking the PI3K/AKT/mTOR might decrease the RPMI-8226 cells which survived the radiotherapy and increase the sensitivity of cells to bortezomib.
METHODS: In this study, the possible mechanism of chemotherapeutic tolerance was preliminarily explored from two aspects: (I) the changes in cell morphology, cell cycle, cell apoptosis, stem cell markers and the signaling transduction pathway after the irradiation of RPMI-8226 cells; (II) the mechanism of enhancing chemotherapeutic sensitivity through the PI3K/AKT/mTOR signaling pathway.
RESULTS: The results showed that the cell morphology and cell cycle of RPMI-8226 had been significantly changed after receiving a radiation dose of 6 Gy in the logarithmic growth phase, the sensitivity of cells to bortezomib had been decreased, the level of stem cell markers had been upregulated, and the PI3K/AKT/mTOR signaling pathway had been activated. However, blocking the PI3K/AKT/mTOR signaling pathway caused the expression of the stem cell markers of RPMI-8226 cells. In addition, the sensitivity of cells to bortezomib had been increased.
CONCLUSIONS: Blocking the PI3K/AKT/mTOR might decrease the RPMI-8226 cells which survived the radiotherapy and increase the sensitivity of cells to bortezomib.
摘要：
背景：本研究旨在探讨多发性骨髓瘤（MM）的耐药机制。
方法：在本研究中，从两个方面初步探讨了化疗耐受的可能机制:(I)细胞形态的改变,细胞周期,细胞凋亡，干细胞标志物和RPMI-8226细胞照射后的信号转导通路；（II）通过PI3K/AKT/mTOR信号通路增强化疗敏感性的机制。
结果：结果表明，RPMI-8226在对数生长期接受6Gy的辐射剂量后，细胞形态和细胞周期发生了显着变化，细胞对硼替佐米的敏感性降低，干细胞标志物水平上调,PI3K/AKT/mTOR信号通路已被激活。然而,阻断PI3K/AKT/mTOR信号通路导致RPMI-8226细胞干细胞标志物的表达。此外,细胞对硼替佐米的敏感性增加。
结论：阻断PI3K/AKT/mTOR可能减少放疗后存活的RPMI-8226细胞，增加细胞对硼替佐米的敏感性。
方法：在本研究中，从两个方面初步探讨了化疗耐受的可能机制:(I)细胞形态的改变,细胞周期,细胞凋亡，干细胞标志物和RPMI-8226细胞照射后的信号转导通路；（II）通过PI3K/AKT/mTOR信号通路增强化疗敏感性的机制。
结果：结果表明，RPMI-8226在对数生长期接受6Gy的辐射剂量后，细胞形态和细胞周期发生了显着变化，细胞对硼替佐米的敏感性降低，干细胞标志物水平上调,PI3K/AKT/mTOR信号通路已被激活。然而,阻断PI3K/AKT/mTOR信号通路导致RPMI-8226细胞干细胞标志物的表达。此外,细胞对硼替佐米的敏感性增加。
结论：阻断PI3K/AKT/mTOR可能减少放疗后存活的RPMI-8226细胞，增加细胞对硼替佐米的敏感性。
