Department of Hematology, 215 Hospital of Shanxi Nuclear Industry, Xianyang, Shanxi 712000, P.R. China.
Oncol Rep. 2020 Feb;43(2):503-515. doi: 10.3892/or.2019.7453. Epub 2019 Dec 31.
Acute lymphoblastic leukemia (ALL) is a malignant hematological disease. Tanshinone IIA (Tan IIA) has antitumor activity in vitro and in vivo. The aim of the present study was to investigate the effects of Tan IIA in combination with imatinib (IM) on the proliferation, apoptosis, migration and invasion of acute T lymphocytic leukemia TIB‑152 cells in vivo and in vitro, and analyze the potential underlying mechanism. Tan IIA and IM, alone and in combination, significantly inhibited proliferation, migration and invasion of TIB‑152 cells, and promoted apoptosis; the effect of co‑treatment with Tan IIA plus IM was enhanced. IGF‑1 promoted the proliferation, migration and invasion of TIB‑152 cells and inhibited apoptosis, while Tan IIA treatment significantly reversed these effects. In vivo experiments demonstrated that treatment with Tan IIA and IM, alone or in combination, significantly inhibited tumor growth in TIB‑152 xenograft mice; the growth inhibition of Tan IIA plus IM was the strongest observed. Western blot analysis revealed that the combination of Tan IIA and IM resulted in significantly lower levels of p‑PI3K, p‑AKT and p‑mTOR in cells and tissues compared with the IM and Tan alone treatment groups. In addition, the combination of Tan IIA and IM significantly decreased the levels of Ki67, cleaved caspase‑3, VEGF and MMP‑9 in cells and tissues, and the level of caspase‑3 was significantly increased. Taken together, the results revealed that Tan IIA enhanced the inhibitory effect of imatinib on TIB‑152 cell proliferation, migration and invasion, and induced apoptosis, which may be associated with inhibition of the PI3K/AKT/mTOR signaling pathway.
急性淋巴细胞白血病（ALL）是一种恶性血液病。丹参酮 IIA（Tan IIA）在体外和体内均具有抗肿瘤活性。本研究旨在探讨 Tan IIA 联合伊马替尼（IM）对急性 T 淋巴细胞白血病 TIB-152 细胞体内外增殖、凋亡、迁移和侵袭的影响，并分析其潜在的作用机制。Tan IIA 和 IM 单独及联合应用均显著抑制 TIB-152 细胞的增殖、迁移和侵袭，促进凋亡；Tan IIA 联合 IM 治疗的效果增强。IGF-1 促进 TIB-152 细胞的增殖、迁移和侵袭，抑制凋亡，而 Tan IIA 处理则显著逆转了这些作用。体内实验表明，Tan IIA 和 IM 单独或联合应用均可显著抑制 TIB-152 移植瘤小鼠的肿瘤生长；Tan IIA 联合 IM 的抑制作用最强。Western blot 分析显示，与单独应用 IM 和 Tan 相比，Tan IIA 联合 IM 可使细胞和组织中 p-PI3K、p-AKT 和 p-mTOR 的水平显著降低。此外，Tan IIA 联合 IM 还可显著降低细胞和组织中 Ki67、cleaved caspase-3、VEGF 和 MMP-9 的水平，同时显著增加 caspase-3 的水平。综上所述，这些结果表明，Tan IIA 增强了伊马替尼对 TIB-152 细胞增殖、迁移和侵袭的抑制作用，并诱导凋亡，这可能与抑制 PI3K/AKT/mTOR 信号通路有关。
