一二三四区视频,亚洲少妇熟女色,日本久热无码视频网,欧美国产日韩大尺度,亚洲a视频,久久少妇一区二区,日韩999无码视频,刺激久久久久久久,啊啊啊啊不要啊在线

ChemicalBook >> journal list >> Drug Design, Development and Therapy >>article
Drug Design, Development and Therapy

Drug Design, Development and Therapy

IF: 4.7
Download PDF

Aprepitant Sensitizes Acute Myeloid Leukemia Cells to the Cytotoxic Effects of Cytosine Arabinoside in vitro and in vivo

Published:18 June 2020 DOI: 10.2147/DDDT.S244648 PMID: 32606608
Hongzhang Wu, Xurui Cheng, Feiyan Huang, Gang Shao, Yueming Meng, Lingfei Wang, Tao Wang, Xiaoyuan Jia, Tianxin Yang, Xi Wang, Caiyun Fu

Abstract

Purpose: Acute myeloid leukemia (AML) is a complex malignancy characterized by the clonal expansion of immature myeloid precursors. The standard treatment for newly diagnosed AML is chemotherapy consisting of cytosine arabinoside (Ara-C) and anthracyclines with disappointing clinical outcomes and severe adverse effects, such as symptomatic bradycardia, neurotoxicity. Thus, it is promising to treat AML through combination drug therapy to reduce the adverse effects of chemotherapeutics. In our recent published PNAS paper, we reported that NK-1R antagonists, both Aprepitant and SR140333, induce apoptosis of myeloid leukemia cells by inducing oxidative stress through mitochondrial calcium overload. We, therefore, tested the hypothesis of the combination Ara-C with NK-1R antagonist could enhance the efficacy of Ara-C.

Methods: MTT assay was employed to detect the cell proliferation. Flow cytometry was applied to detect the cell cycle and necrosis. PI uptake and LDH release assay were used to detect the disintegration of the plasma membrane. Xenograft model was constructed to explore the effect of combination Ara-C with Aprepitant in vivo.

Results: Our results showed that Aprepitant sensitizes HL60 cells to the cytotoxic effects of Ara-C more than 5-fold by enhancing G0/G1 cell cycle arrest and necrosis in vitro. Furthermore, Nec-1, a specific inhibitor of necroptosis, could recover the cell proliferative viability significantly. Attractively, once every 2-days regimen of Ara-C (5 mg/kg) and Aprepitant (10 mg/kg) via in situ injection dramatically reduced the tumor volume from 2175.0 ± 341.9 mm3 in the vehicle group to 828.4 ± 232.4 mm3 in the combination group without obvious toxicity in human myeloid leukemia xenograft mice.

Conclusion: Taken together, reduced dose of Ara-C combination with moderate Aprepitant provides more effective therapeutical methods for AML treatment in vitro and in vivo with the elimination of the toxicity of Ara-C, which may pay new avenue for the usage of the routine chemotherapy drug Ara-C with low dose to enhance efficacy and reduce toxicity in clinical practice.

Substances (5)

Materials Related products
Procduct Name CAS Molecular Formula Supplier Price
Necrostatin-1 4311-88-0 C13H13N3OS 262 suppliers $12.00-$3635.00
Necrostatin-1 4311-88-0 C13H13N3OS 262 suppliers $12.00-$3635.00
Necrostatin-1 4311-88-0 C13H13N3OS 262 suppliers $12.00-$3635.00
Necrostatin-1 4311-88-0 C13H13N3OS 262 suppliers $12.00-$3635.00

Similar articles

IF:4.6

In Vitro and In Vivo Neuroprotective Effects of Sarcosine.

ACS Applied Bio Materials Arzugül Tanas, ?zlem ?zdemir Tozlu,etc Published: 15 October 2022
IF:6.8

The ways for ginsenoside Rh2 to fight against cancer: the molecular evidences in?vitro and in?vivo.

Journal of Ginseng Research Qi-rui Hu , Yao Pan ,etc Published: 1 March 2023
IF:1.2

Successful hyaluronic acid filler injection in a chronic myeloid leukemia patient taking imatinib mesylate.

Journal of Cosmetic and Laser Therapy Yegyu Sung, Min Hee Kim,etc Published: 1 January 2019
辉南县| 夏津县| 沁阳市| 江北区| 卓尼县| 邢台县| 云林县| 舒城县| 玉屏| 隆德县| 云和县| 峨边| 江安县| 耒阳市| 罗江县| 新乡县| 龙川县| 塔城市| 衡山县| 河曲县| 青神县| 临颍县| 石泉县| 聂拉木县| 都江堰市| 济源市| 姜堰市| 邓州市| 甘谷县| 云安县| 西宁市| 都安| 伊春市| 怀远县| 云龙县| 石门县| 如皋市| 个旧市| 海门市| 江阴市| 包头市|