Inhibitory Effect of Ouabain on Resistance to Imatinib in Chronic Myeloid Leukemia K562/G01 Cells

作者全名："Sun, Chang; Liu, J.; Zhai, Shiqi; Liu, H.; Peng, L.; Hu, Jing"

作者地址："[Sun, Chang; Zhai, Shiqi] Chongqing Med Univ, Clin Coll 1, Chongqing 400016, Peoples R China; [Liu, J.; Liu, H.; Peng, L.] Chongqing Med Univ, Coll Stomatol, Chongqing 400016, Peoples R China; [Hu, Jing] Chongqing Med Univ, Fac Laboratorial Med, Key Lab Med Diagnost, Minist Educ, Chongqing 400016, Peoples R China"

通信作者："Hu, J (通讯作者)，Chongqing Med Univ, Fac Laboratorial Med, Key Lab Med Diagnost, Minist Educ, Chongqing 400016, Peoples R China."

来源：INDIAN JOURNAL OF PHARMACEUTICAL SCIENCES

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001027246400008

JCR分区：Q4

影响因子：0.4

年份：2023

卷号：85

期号：3

开始页：621

结束页：631

文献类型：Article

关键词：Chronic myeloid leukemia; ouabain; imatinib-resistance; toxicity

摘要："Ouabain has shown powerful anti-proliferation activities in various cancers, but its effect on imatinibresistant chronic myeloid leukemia and toxicity on normal mice has not been investigated. Cell Counting Kit-8 assay was used to detect cytotoxicity and reversal effect of ouabain with different concentration (0.01 & mu;M, 0.1 & mu;M, 1.0 & mu;M, 10 & mu;M) on drug resistance of imatinib-resistant cell line of chronic myeloid leukemia (K562/G01 cell line). Flow cytometry was used to detect the apoptosis effect and cell cycle arrest. Hematological examination, biochemical examination and histological examination were used to detect sub-chronic toxicity of ouabain on healthy mice. In our present study, ouabain showed greatly inhibitory effect and significantly reduced half minimal inhibitory concentration of imatinib in K562/ G01 cells, an imatinib-resistant cell line of chronic myeloid leukemia, in a dose- and time- dependent manner, which implied that ouabain increased cell sensitivity to imatinib. Ouabain enhanced apoptosis induced by imatinib in K562/G01 cells not through cell cycle arrest. Animal experiments showed that there were no significant variances in hematological, liver function, kidney function parameters and organ histopathology of all mice groups. These data suggested that ouabain could be a potential agent to treat imatinib-resistant chronic myeloid leukemia for its powerful cytotoxicity as well as reversal effect, but further study is needed to find out its specific mechanism."

基金机构：Natural Science Foundation of Chongqing [CSTB2022NSCQ-MSX0764]; College Students Innovative Experimental Program of Chongqing Medical University [SRIEP202010]

基金资助正文："This study was supported by the Natural Science Foundation of Chongqing (CSTB2022NSCQ-MSX0764) , and the College Students Innovative Experimental Program of Chongqing Medical University (SRIEP202010) ."