<br>PI3K/mTOR双重抑制剂PF-04979064调节胃癌肿瘤生长并增强胃癌细胞对5-FU的药物敏感性,Biomedicine & Pharmacotherapy

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PI3K/mTOR双重抑制剂PF-04979064调节胃癌肿瘤生长并增强胃癌细胞对5-FU的药物敏感性
Biomedicine & Pharmacotherapy ( IF 6.9 ) Pub Date : 2023-12-29 , DOI: 10.1016/j.biopha.2023.116086
Ziyuan Zhong ₁ , Tengkai Wang ₂ , Ruochen Zang ₃ , Yufei Zang ₄ , Yaoyao Feng ₄ , Shujun Yan ₅ , Congcong Geng ₄ , Na Zhu ₅ , Qian Wang ₆

Affiliation

胃癌（GC）具有肿瘤异质性高、手术难度增加、化疗疗效有限等特点，预后不良。细胞的异常增殖涉及PI3K/AKT/mTOR信号通路的异常激活。抑制该信号通路可以抑制肿瘤细胞增殖并诱导细胞凋亡。本研究评估了 PI3K 和 mTOR 双重抑制剂 PF-04979064 对人 GC 细胞的影响。 PF-04979064显着抑制人胃腺癌AGS细胞和未分化GC细胞系HGC-27的增殖，促进细胞凋亡。 PF-04979064与GC一线临床药物5-FU联合治疗显示出协同作用，PF-04979064显着增加GC细胞对化疗药物的敏感性。 Western blot 结果显示，PF-04979064 显着抑制 GC 细胞中的 PI3K/AKT/mTOR 信号通路，而 RNA seq 结果表明，用 PF-04979064 处理后，基因表达谱发生了显着变化。这项研究深入了解了 PF-04979064 的作用，从而为其治疗 GC 的潜在临床应用奠定了坚实的基础。

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Dual PI3K/mTOR inhibitor PF-04979064 regulates tumor growth in gastric cancer and enhances drug sensitivity of gastric cancer cells to 5-FU

Gastric cancer (GC) is characterized by high tumor heterogeneity, increased surgical difficulty, and limited chemotherapy efficacy, and it is associated with a poor prognosis. The abnormal proliferation of cells involves abnormal activation of the PI3K/AKT/mTOR signaling pathway. Inhibition of this signaling pathway can inhibit tumor cell proliferation and induce cell apoptosis. This study evaluated the effect of PF-04979064, a dual inhibitor of PI3K and mTOR, on human GC cells. PF-04979064 significantly inhibited the proliferation of human gastric adenocarcinoma AGS cells and the undifferentiated GC cell line HGC-27, promoting cell apoptosis. Combination treatment with PF-04979064 and the GC first-line clinical drug 5-FU showed synergistic effects, and PF-04979064 markedly increased the sensitivity of GC cells to chemotherapy drugs. Western blot results showed that PF-04979064 significantly inhibited the PI3K/AKT/mTOR signaling pathway in GC cells, whereas RNA seq results demonstrated substantial alterations in gene expression profiles upon treatment with PF-04979064. This study provides insight into the effects of PF-04979064, thereby establishing a solid foundation for its potential clinical application in the treatment of GC.

更新日期：2023-12-29

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